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  • United plane clips tail of another aircraft at Chicago’s O’Hare airport | United Airlines

    United plane clips tail of another aircraft at Chicago’s O’Hare airport | United Airlines

    A United Airlines plane heading for its gate clipped the tail of another United aircraft at Chicago’s O’Hare airport, authorities said.

    No one was hurt in Friday’s incident, and the 113 passengers on flight 2652 from Jackson Hole, Wyoming, were able to leave the plane normally after a delay, United officials said in a statement.

    Runway collisions like these could add to worries about aviation safety in the wake of recent crashes and near misses – including the deadliest plane crash in the United States in decades, when an army helicopter collided with an airliner preparing to land at Ronald Reagan Washington National airport in January.

    Earlier in October, two Delta Air Lines regional jets collided at the intersection of taxiways at LaGuardia airport in New York, injuring a flight attendant.

    In Friday’s case, the second United plane had its horizontal stabilizer struck and was not moving when the planes hit, officials said.

    Bill Marcus, a passenger on the flight from Wyoming, said he didn’t even realize anything happened until the pilot said there would be a delay to document something and passengers on the plane saw a number of people gather around the right wing.

    “I was shocked that I didn’t feel something more, although when they separated the planes there was some shuddering,” Marcus told CBS News Chicago. It took about 40 extra minutes for the plane to get to the gate, he said.

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  • Bailey warns of long-lasting growth drag from Brexit

    Bailey warns of long-lasting growth drag from Brexit

    Stay informed with free updates

    Brexit will have a negative impact on the UK economy for the “foreseeable future”, the Bank of England governor has warned,…

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  • ENHERTU® (fam-trastuzumab deruxtecan-nxki) reduced the risk of disease recurrence or death by 53% vs. T-DM1 in patients with high-risk HER2-positive early breast cancer following neoadjuvant therapy in DESTINY-Breast05 Phase III trial

    Positive results from the DESTINY-Breast05 Phase III trial showed ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) in patients with a high risk of disease recurrence. The trial compared ENHERTU with trastuzumab emtansine (T-DM1) as a post-neoadjuvant treatment (after surgery) in patients with HER2-positive early breast cancer with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant treatment.

    Results showed ENHERTU significantly reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1 as a post-neoadjuvant treatment (based on an IDFS hazard ratio [HR] of 0.47, 95% confidence interval [CI] 0.34-0.66, p<0.0001). At three years, 92.4% of patients in the ENHERTU arm were alive and free of invasive disease, compared with 83.7% of those in the T-DM1 arm. The IDFS results were consistent across all prespecified subgroups.

    ENHERTU also significantly reduced the risk of disease recurrence or death (disease-free survival [DFS]), a key secondary endpoint, by 53% (HR 0.47; 95% CI 0.34-0.66; p<0.0001).  Further, ENHERTU lowered the risk of distant disease recurrence (distant recurrence-free interval [DRFI]) by 51% and the risk of brain metastases (brain metastasis-free interval [BMFI]) by 36% versus T-DM1.

    Overall survival (OS) was not mature at the time of this planned interim analysis (2.9% maturity at data cut-off) and will be assessed in future analyses (HR 0.61; 95% CI 0.34-1.10).

    Charles Geyer, MD, Chief Scientific Officer of the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP) Foundation, Professor of Medicine at the UPMC Hillman Cancer Center and principal investigator for the trial, said: “For patients with residual disease after neoadjuvant treatment, the post‑neoadjuvant setting represents a critical second opportunity to reduce recurrence risk, and in DESTINY‑Breast05 ENHERTU reduced the risk of early recurrence or death by 53 percent compared to the current standard of T‑DM1. These results, coupled with the safety data from the trial, are likely to transform clinical practice in the post-neoadjuvant setting for patients with high-risk disease, with the potential for ENHERTU to set a new standard of care.”

    Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Progress in treating HER2-positive early breast cancer has been significant, yet managing patients at a higher-risk of recurrence remains challenging. These landmark data, alongside those from DESTINY-Breast11, underscore the potential of ENHERTU to become a foundational treatment in early-stage breast cancer, increasing the likelihood that more patients could be cured in this setting.”

    Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The results of DESTINY-Breast05 demonstrate a clear benefit of ENHERTU over the current standard of care in patients with high-risk HER2-positive early breast cancer following surgery, improving their chance for sustained long-term outcomes. These results, coupled with the results of DESTINY-Breast11, illustrate the continued promise of ENHERTU to move earlier in the breast cancer treatment paradigm where it can have the greatest impact on the lives of patients.”

    Summary of Results: DESTINY-Breast05i

    Efficacy Measure

    ENHERTU
    (5.4 mg/kg; n=818)

    T-DM1
    (n=817)

    IDFSii

    3-year IDFS rate, %

    92.4

    83.7

     

    HR 0.47 (95% CI 0.34-0.66); p<0.0001

    DFSiii

    3-year DFS rate, %

    92.3

    83.5

     

    HR 0.47 (95% CI 0.34-0.66); p<0.0001

    DRFIiv

    3-year event-free rate, %

    93.9

    86.1

     

    HR 0.49 (95% CI 0.34-0.71)

    BMFIv

    3-year event-free rate, %

    97.6

    95.8

     

    HR 0.64 (95% CI 0.35-1.17)

    OSvi

    Survival at 3 years, %

    97.4

    95.7

     

    HR 0.61 (95% CI 0.34-1.10)

    TDM-1, trastuzumab emtansine; CI, confidence interval; HR, hazard ratio; IDFS, invasive disease-free survival; DFS, disease-free survival; DRFI, distant recurrence-free interval; BMFI, brain-metastasis-free interval; OS, overall survival

    i Data cut-off July 2, 2025

    ii IDFS is defined as the time from randomization until the date of first occurrence of one of the following events: recurrence of ipsilateral invasive breast tumor, recurrence of ipsilateral locoregional invasive breast cancer, contralateral invasive breast cancer, a distant disease recurrence or death from any cause; based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure

    iii DFS is defined as the time between randomization and the date of the first occurrence of an IDFS event per STEEP criteria, including second primary non-breast cancer event, or contralateral or ipsilateral ductal carcinoma in situ (DCIS); based on investigator assessment; statistically evaluated using the pre-specified hierarchical testing procedure

    iv DRFI is defined as the time between randomization and the date of distant breast cancer recurrence; based on investigator assessment

    v BMFI is defined as the time between randomization and the date of documentation of brain metastases or leptomeningeal disease; based on investigator assessment

    vi 2.9% maturity

    The safety profile of ENHERTU observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified. Grade 3 or higher treatment emergent adverse events (AEs) rates were comparable between ENHERTU and T-DM1 (50.6% versus 51.9%). Rates of interstitial lung disease (ILD) were low in both arms with ILD events occurring in 9.6% of the ENHERTU arm and 1.6% of the T-DM1 arm. The majority of ILD events were low Grade (Grade 1 or 2). There were no Grade 3 or higher ILD events for T-DMI. There were seven Grade 3 events and no Grade 4 events in the ENHERTU arm. There were two Grade 5 events in the ENHERTU arm as determined by an independent adjudication committee.

    The DESTINY-Breast05 results (abstract #LBA1) will be presented today during Presidential Symposium I alongside the results of the DESTINY-Breast11 Phase III trial (abstract #291O) at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.

    DESTINY-Breast05 was conducted in collaboration with the NSABP, the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group.

    ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

    IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab deruxtecan-nxki)

    Indications

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

    • Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
    • Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

    Contraindications
    None.

    Warnings and Precautions
    Interstitial Lung Disease / Pneumonitis

    Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

    HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

    In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.

    HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

    In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

    Neutropenia

    Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.

    HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

    In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1.2% of patients.

    HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

    In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

    Left Ventricular Dysfunction

    Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

    HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

    In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.

    HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

    In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

    Embryo-Fetal Toxicity
    ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.

    Additional Dose Modifications

    Thrombocytopenia

    For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.

    Adverse Reactions

    HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

    The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).

    HER2-Positive Metastatic Breast Cancer

    DESTINY-Breast03
    The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.

    Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).

    ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).

    HER2-Low and HER2-Ultralow Metastatic Breast Cancer

    DESTINY-Breast06

    The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.

    Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).

    ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).

    DESTINY-Breast04

    The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

    Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

    ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).

    HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)

    DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.

    The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY-Lung02. Nineteen percent of patients were exposed for >6 months.

    Serious adverse reactions occurred in 30% of patients receiving ENHERTU.Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%).

    ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%).

    HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

    The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.

    Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%).

    ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).

    HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors

    The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).

    Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock.

    ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).

    Use in Specific Populations

    • Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
    • Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
    • Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
    • Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
    • Geriatric Use: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg, 24% were ≥65 years and 4.9% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (61%) as compared to younger patients (52%). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were ≥65 years and 9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
    • Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
    • Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

    To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

    Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

    Notes

    Post neoadjuvant treatment for HER2-positive early breast cancer

    Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.1

    HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast cancer.2 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

    For patients with HER2-positive early breast cancer, achieving pCR with neoadjuvant treatment is the earliest indicator of improved long-term survival.4 However, approximately half of patients who receive neoadjuvant treatment do not reach pCR and have poorer long-term outcomes, putting them at increased risk of disease recurrence.5-9

    Post-neoadjuvant therapy represents a key opportunity to minimize the risk of recurrence and prevent progression to metastatic disease for patients with residual disease. Despite receiving additional treatment with T-DMI in the post-neoadjuvant setting, approximately 20% of patients still experience invasive disease or death and no reduction in the risk of CNS recurrence.10,11 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90% to approximately 30%.12

    New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.

    DESTINY-Breast05

    DESTINY-Breast05 is a global, multicenter, randomized, open-label, Phase III trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2-positive early breast cancer with residual invasive disease in breast and/or axillary lymph nodes following neoadjuvant therapy and a high risk of recurrence. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy.

    The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomization until first recurrence, distant recurrence or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include OS, distant recurrence-free interval, brain metastases-free interval and safety.

    DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

    ENHERTU

    ENHERTU is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2-monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

    ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

    ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

    ENHERTU (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

    ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

    ENHERTU (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

    ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

    ENHERTU development program

    A comprehensive global clinical development programme is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

    Daiichi Sankyo collaboration

    AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan-dlnk in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan-dlnk.

    AstraZeneca in breast cancer
    Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

    AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment.

    With ENHERTU, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings.

    In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines fulvestrant and goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, the TROP2-directed ADC, datopotamab deruxtecan-dlnk, and next-generation oral SERD and potential new medicine camizestrant.

    PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with Merck & Co., Inc. (known as MSD outside the US and Canada) continue to research olaparib in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer.

    To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of datopotamab deruxtecan-dlnk alone and in combination with immunotherapy durvalumab.

    AstraZeneca in oncology

    AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

    The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

    AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on Social Media @AstraZeneca.

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    2. Eli Lilly Makes A Bold Claim For Its Biggest Cancer Drug  Investor’s Business Daily
    3. Abemaciclib Plus Endocrine Therapy Improves Overall Survival in High-Risk Early Breast Cancer  The American Journal of Managed Care® (AJMC®)
    4. Eli Lilly Says Verzenio Reduced Risk of Death In Late-Stage Trial In Some Breast Cancer Patients  Stocktwits
    5. ESMO25: Battle lines drawn with updates for Lilly, Novartis CDK4/6 inhibitors  FirstWord Pharma

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    Louis Tomlinson gets honest about grieving Liam Payne

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    Louis Tomlinson has opened up about the emotional aftermath of Liam Payne’s tragic untimely death.

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  • PADCEV™ Plus KEYTRUDA™, Given Before and After Surgery, Cuts the Risk of Recurrence, Progression or Death by 60% and the Risk of Death by 50% for Certain Patients with Bladder Cancer

    PADCEV™ Plus KEYTRUDA™, Given Before and After Surgery, Cuts the Risk of Recurrence, Progression or Death by 60% and the Risk of Death by 50% for Certain Patients with Bladder Cancer

    • First and only combination regimen to improve survival when used before and after surgical cystectomy in cisplatin-ineligible patients with muscle-invasive bladder cancer
    • Unprecedented survival results from pivotal Phase 3 EV-303 trial show potential for PADCEV plus KEYTRUDA to redefine standard of care

    TOKYO and NEW YORK, Oct. 18, 2025 /PRNewswire/ — Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) and Pfizer Inc. (NYSE: PFE) today announced positive results from the pivotal Phase 3 EV-303 clinical trial (also known as KEYNOTE-905) for PADCEV™ (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, in combination with KEYTRUDA™ (pembrolizumab), a PD-1 inhibitor. The study evaluated the combination in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or declined cisplatin-based chemotherapy. PADCEV plus KEYTRUDA significantly improved event-free survival (EFS) and overall survival (OS) when used as a neoadjuvant and adjuvant treatment (before and after surgery) versus the current standard of care—surgery alone. Results from the EV-303 trial will be presented today in a Presidential Symposium (Abstract #LBA2) at the 2025 European Society of Medical Oncology (ESMO) Congress in Berlin, Germany.

    At the first interim efficacy analysis, results from the primary endpoint of EFS showed a 60% reduction in the risk of tumor recurrence, progression or death for patients treated with neoadjuvant and adjuvant PADCEV plus KEYTRUDA as compared to surgery alone (Hazard Ratio (HR) of 0.40; 95% Confidence Interval (CI), 0.28-0.57; p<0.0001). The estimated median EFS has not yet been reached for the combination arm versus 15.7 months for the surgery alone arm. An estimated 74.7% of patients treated with the combination were event free at two years, relative to 39.4% of patients who received surgery only.

    Results from the key secondary endpoint of OS showed a 50% reduction in the risk of death for neoadjuvant and adjuvant PADCEV plus KEYTRUDA as compared to surgery alone (HR of 0.50; 95% CI, 0.33-0.74; p<0.0002). The estimated median OS has not yet been reached for the combination arm versus 41.7 months for the surgery arm. An estimated 79.7% of patients were alive at two years relative to 63.1% of patients who received surgery only.

    Consistent EFS and OS benefits were seen across all pre-defined subgroups, including age, gender, smoking status and PD-L1 status as well as protocol-defined stratification groups based on cisplatin ineligibility (ineligible vs eligible but declined), clinical stage and geographic region.

    The safety results in EV-303 were consistent with those previously reported for this combination. The most common (≥30%) adverse events (AEs) reported in the neoadjuvant and adjuvant PADCEV plus KEYTRUDA arm were pruritus (itching), alopecia, diarrhea, fatigue and anemia. Grade ≥ 3 AEs due to any cause occurred in 71.3% of patients treated in the combination arm and 45.9% of patients who received surgery only.

    Christof Vulsteke, M.D., Ph.D., Head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent and EV-303 Principal Investigator
    “For decades, patients with muscle-invasive bladder cancer who are ineligible for cisplatin treatment have faced limited treatment options, often relying on surgery alone. The groundbreaking benefits seen in the KEYNOTE-905/EV-303 trial at this early interim analysis position the pembrolizumab and enfortumab vedotin combination to fundamentally change the way we approach the treatment of patients with this disease.”

    For the secondary endpoint of pathologic complete response (pCR), treatment with neoadjuvant PADCEV plus KEYTRUDA demonstrated a 57.1% pCR rate versus an 8.6% pCR rate for patients who received surgery only (estimated difference 48.3%; 95% CI 39.5-56.5; p<0.000001).

    Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas
    “The compelling EV-303 results may establish a new efficacy benchmark in muscle-invasive bladder cancer. For the first time, a systemic treatment approach used before and after surgery has improved survival over standard surgery in cisplatin-ineligible patients. These data underscore the transformative potential of PADCEV plus KEYTRUDA as we continue to explore this combination in a broad population of patients with muscle-invasive bladder cancer.”

    Jeff Legos, Ph.D., M.B.A., Chief Oncology Officer, Pfizer
    “The ability of PADCEV plus KEYTRUDA to reduce the risk of death by half in this setting is a remarkable advancement for patients who have seen limited treatment options and often face poor prognosis. These unprecedented results suggest that the transformational efficacy of this combination in advanced bladder cancer may extend into an earlier disease setting, potentially providing a life-changing impact for patients.”

    Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally.1 MIBC represents approximately 30% of all bladder cancer cases.2 The standard treatment for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery, which has been shown to prolong survival.3 However, up to half of patients with MIBC are not eligible to receive cisplatin and face limited treatment options, typically undergoing surgery without any systemic treatment.3

    PADCEV plus KEYTRUDA is not currently approved for use as neoadjuvant and adjuvant treatment in cisplatin-ineligible patients with MIBC. These results will be discussed with global health authorities for potential regulatory filings. Neoadjuvant and adjuvant PADCEV plus KEYTRUDA is also being evaluated in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 clinical trial (also known as KEYNOTE-B15).

    The EV-303 trial is continuing to evaluate the secondary EFS, OS and pCR rate endpoints for neoadjuvant and adjuvant KEYTRUDA monotherapy versus surgery alone as they continue to mature.

    About the EV-303/KEYNOTE-905 Trial
    The EV-303 trial (also known as KEYNOTE-905) is an ongoing, open-label, randomized, three-arm, controlled, Phase 3 study evaluating neoadjuvant and adjuvant PADCEV plus KEYTRUDA or neoadjuvant and adjuvant KEYTRUDA versus surgery alone in patients with MIBC who are either not eligible for or declined cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant KEYTRUDA (arm A), surgery alone (arm B) or neoadjuvant and adjuvant PADCEV plus KEYTRUDA (arm C).4

    The primary endpoint of this trial is EFS between arm C and arm B, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) surgery or failure to undergo RC surgery in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence as assessed by imaging and/or biopsy or death due to any cause. Key secondary endpoints include OS and pCR rate between arm C and arm B, as well as EFS, OS and pCR rate between arm A and arm B.4

    For more information on the global EV-303 trial, go to clinicaltrials.gov.

    About PADCEV™ (enfortumab vedotin)
    PADCEV™ (enfortumab vedotin) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6

    PADCEV plus KEYTRUDA is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) regardless of cisplatin eligibility in the United States, Japan, and a number of other countries around the world. In the European Union, the combination is approved for the treatment of adult patients with la/mUC who are eligible for platinum-containing chemotherapy. PADCEV is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.6

    PADCEV® (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information 

    BOXED WARNING: SERIOUS SKIN REACTIONS

    • PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
    • Closely monitor patients for skin reactions.
    • Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
    • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Indication 
    PADCEV®, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC).

    PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or mUC who:

    • have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
    • are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

    PADCEV Important Safety Information

    Warnings and Precautions

    Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 70% (all grades) of the 564 patients treated with PADCEV in combination with pembrolizumab in clinical trials. When PADCEV was given in combination with pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate compared to PADCEV as a single agent. The majority of the skin reactions that occurred with combination therapy included maculo-papular rash, macular rash and papular rash. Grade 3-4 skin reactions occurred in 17% of patients (Grade 3: 16%, Grade 4: 1%), including maculo-papular rash, bullous dermatitis, dermatitis, exfoliative dermatitis, pemphigoid, rash, erythematous rash, macular rash, and papular rash. A fatal reaction of bullous dermatitis occurred in one patient (0.2%). The median time to onset of severe skin reactions was 1.7 months (range: 0.1 to 17.2 months). Skin reactions led to discontinuation of PADCEV in 6% of patients.

    Skin reactions occurred in 58% (all grades) of the 720 patients treated with PADCEV as a single agent in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 34% had pruritus. Grade 3-4 skin reactions occurred in 14% of patients, including maculo-papular rash, erythematous rash, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. The median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 8 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=75), 24% of patients restarting at the same dose and 24% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 3.1% of patients.

    Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. For persistent or recurrent Grade 2 skin reactions, consider withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for Grade 3 skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

    Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials of PADCEV as a single agent, 17% of the 720 patients treated with PADCEV developed hyperglycemia of any grade; 7% of patients developed Grade 3-4 hyperglycemia (Grade 3: 6.5%, Grade 4: 0.6%). Fatal events of hyperglycemia and DKA occurred in one patient each (0.1%). The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. The median time to onset of hyperglycemia was 0.5 months (range: 0 to 20 months). Hyperglycemia led to discontinuation of PADCEV in 0.7% of patients. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. Of the patients who initiated insulin therapy for treatment of hyperglycemia, 66% (23/35) discontinued insulin at the time of last evaluation. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

    Pneumonitis/Interstitial Lung Disease (ILD) Severe, life-threatening or fatal pneumonitis/ILD occurred in patients treated with PADCEV. When PADCEV was given in combination with pembrolizumab, 10% of the 564 patients treated with combination therapy had pneumonitis/ILD of any grade and 4% had Grade 3-4. A fatal event of pneumonitis/ILD occurred in two patients (0.4%). The incidence of pneumonitis/ILD, including severe events, occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent. The median time to onset of any grade pneumonitis/ILD was 4 months (range: 0.3 to 26 months).

    In clinical trials of PADCEV as a single agent, 3% of the 720 patients treated with PADCEV had pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median time to onset of any grade pneumonitis/ILD was 2.9 months (range: 0.6 to 6 months).

    Monitor patients for signs and symptoms indicative of pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis/ILD.

    Peripheral neuropathy (PN) When PADCEV was given in combination with pembrolizumab, 67% of the 564 patients treated with combination therapy had PN of any grade, 36% had Grade 2 neuropathy, and 7% had Grade 3 neuropathy. The incidence of PN occurred at a higher rate when PADCEV was given in combination with pembrolizumab compared to PADCEV as a single agent. The median time to onset of Grade ≥2 PN was 6 months (range: 0.3 to 25 months).

    PN occurred in 53% of the 720 patients treated with PADCEV as a single agent in clinical trials including 38% with sensory neuropathy, 8% with muscular weakness and 7% with motor neuropathy. Thirty percent of patients experienced Grade 2 reactions and 5% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without preexisting PN. The median time to onset of Grade ≥2 PN was 4.9 months (range: 0.1 to 20 months). Neuropathy led to treatment discontinuation in 6% of patients.

    Monitor patients for symptoms of new or worsening PN and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 PN.

    Ocular disorders were reported in 40% of the 384 patients treated with PADCEV as a single agent in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 30% of patients, and blurred vision occurred in 10% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.7 months (range: 0 to 30.6 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

    Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 720 patients treated with PADCEV as a single agent in clinical trials, 1% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

    Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

    ADVERSE REACTIONS

    Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV in combination with pembrolizumab)
    Increased aspartate aminotransferase (AST), increased creatinine, rash, increased glucose, PN, increased lipase, decreased lymphocytes, increased alanine aminotransferase (ALT), decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection and decreased platelets.

    Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV monotherapy)
    Increased glucose, increased AST, decreased lymphocytes, increased creatinine, rash, fatigue, PN, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased ALT, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, dry skin.

    EV-302 Study: 440 patients with previously untreated la/mUC (PADCEV in combination with pembrolizumab)
     Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab. The most common serious adverse reactions (≥2%) were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Fatal adverse reactions occurred in 3.9% of patients treated with PADCEV in combination with pembrolizumab including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).

    Adverse reactions leading to discontinuation of PADCEV occurred in 35% of patients. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were PN (15%), rash (4.1%) and pneumonitis/ILD (2.3%). Adverse reactions leading to dose interruption of PADCEV occurred in 73% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were PN (22%), rash (16%), COVID19 (10%), diarrhea (5%), pneumonitis/ILD (4.8%), fatigue (3.9%), hyperglycemia (3.6%), increased ALT (3%) and pruritus (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 42% of patients. The most common adverse reactions (≥2%) leading to dose reduction of PADCEV were rash (16%), PN (13%) and fatigue (2.7%).

    EV-103 Study: 121 patients with previously untreated la/mUC who were not eligible for cisplatin-containing chemotherapy (PADCEV in combination with pembrolizumab)
     Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with pembrolizumab; the most common (≥2%) were acute kidney injury (7%), urinary tract infection (7%), urosepsis (5%), sepsis (3.3%), pneumonia (3.3%), hematuria (3.3%), pneumonitis/ILD (3.3%), urinary retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%), myositis (2.5%), anemia (2.5%), and hypotension (2.5%). Fatal adverse reactions occurred in 5% of patients treated with PADCEV in combination with pembrolizumab, including sepsis (1.6%), bullous dermatitis (0.8%), myasthenia gravis (0.8%), and pneumonitis/ILD (0.8%). Adverse reactions leading to discontinuation of PADCEV occurred in 36% of patients; the most common (≥2%) were PN (20%) and rash (6%). Adverse reactions leading to dose interruption of PADCEV occurred in 69% of patients; the most common (≥2%) were PN (18%), rash (12%), increased lipase (6%), pneumonitis/ILD (6%), diarrhea (4.1%), acute kidney injury (3.3%), increased ALT (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract infection (3.3%), increased amylase (2.5%), anemia (2.5%), COVID19 (2.5%), hyperglycemia (2.5%), and hypotension (2.5%). Adverse reactions leading to dose reduction of PADCEV occurred in 45% of patients; the most common (≥2%) were PN (17%), rash (12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%).

    EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy (PADCEV monotherapy)
     Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each), and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis/ILD, and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%), and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite, and fatigue (3% each).

    EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for cisplatin-based chemotherapy (PADCEV monotherapy)
     Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥3%) were pneumonia, sepsis, and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia, and pneumonitis/ILD (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), increased AST, and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%), and fatigue (7%).

    DRUG INTERACTIONS
    Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)
    Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

    SPECIFIC POPULATIONS
    Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for 3 weeks after the last dose.

    Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

    For more information, please see the U.S. full Prescribing Information including BOXED WARNING for PADCEV here .

    About Astellas
    Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women’s health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at www.astellas.com.

    About Pfizer Oncology
    At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.

    About the Pfizer, Astellas and Merck Collaboration
    Seagen and Astellas previously entered a clinical collaboration agreement with Merck to evaluate the combination of Seagen’s and Astellas’ PADCEV™ (enfortumab vedotin) and Merck’s KEYTRUDA™ (pembrolizumab) in patients with muscle-invasive bladder cancer (MIBC) who are not eligible for or declined cisplatin-based chemotherapy. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).

    Astellas Cautionary Notes
     In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’ intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

    Pfizer Disclosure Notice
     The information contained in this release is as of October 18, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or fu ture events or developments.

    This release contains forward-looking information about Pfizer Oncology and PADCEV™ (enfortumab vedotin) in combination with pembrolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer, including their potential benefits and plans to present the Phase 3 EV-303 clinical trial results at the 2025 European Society of Medical Oncology Congress and discuss the Phase 3 EV-303 clinical trial results with global health authorities for potential regulatory filings that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risk and uncertainties include, among other things, uncertainties regarding the commercial  success of enfortumab vedotin; the uncertainties inherent in research and development, including the a bility to meet anticipated clinical endpoints (and continuing evaluation of endpoints), commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory autho rities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any applications may be filed with regulatory authorities in particular jurisdictions for any potential indication for enfortumab vedotin with pembrolizumab or as a single agent ; whether and when any applications that may be pending or filed for enfortumab vedotin with pembrolizumab or as a single agent  may be approved by regulatory authorities, which will depend on myriad factors, inclu ding making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether enfortumab vedotin with pembrolizumab or as a single agent will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of enfortumab vedotin with pembrolizumab or as a single agent; whether the collaboration between Pfizer, Astellas and Merck will be successful; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments.

    A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov  and www.pfizer.com .

    1 World Bladder Cancer Patient Coalition. GLOBOCAN 2022: Bladder cancer 9th most common worldwide. Accessed October 16, 2025. Available at: https://worldbladdercancer.org/news_events/globocan-2022-bladder-cancer-is-the-9th-most-commonly-diagnosed-worldwide/

    2 Bladder Cancer Awareness Network. What is Muscle Invasive Bladder Cancer? Accessed October 16, 2025. Available at: https://bcan.org/what-is-muscle-invasive-bladder-cancer/#:~:text=When%20tumors%20grow%20into%20or,Virginia%20Health%20System%20explain%20MIBC.

    3 Esteban-Villarrubia J, Torres-Jiménez J, Bueno-Bravo C, García-Mondaray R, Subiela JD, Gajate P. Current and Future Landscape of Perioperative Treatment for Muscle-Invasive Bladder Cancer. Cancers (Basel). 2023 Jan 17;15(3):566. doi: 10.3390/cancers15030566. PMID: 36765525; PMCID: PMC9913718.

    4 National Institute of Health. National Library of Medicine. Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303. ClinicalTrials.gov identifier: NCT03924895. Published July 24, 2019. Updated June 17, 2025. Accessed October 16, 2025. Available at: https://clinicaltrials.gov/study/NCT03924895?term=AREA%5BBasicSearch%5D(myosarcoma)&rank=3

    5 Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 2016;76(10):3003-13.

    6 PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc.

    SOURCE Astellas Pharma Inc.

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  • Tarlatamab Plus Chemo/IO Regimens Are Safe, Elicit Responses in ES-SCLC

    Tarlatamab Plus Chemo/IO Regimens Are Safe, Elicit Responses in ES-SCLC

    Tarlatamab plus frontline chemoimmunotherapy and PD-L1 maintenance therapy demonstrated both encouraging safety and clinical outcomes in patients with extensive-stage (ES) small cell lung cancer (SCLC), according to cohort results of the phase 1b DeLLphi-303 study (NCT05361395) that were presented during the European Society for Medical Oncology Congress 2025 and simultaneously published in The Lancet Oncology.1,2

    At a median follow-up of 13.8 months (95% CI, 12.5-15.0), the objective response rate (ORR) was 71% (95% CI, 61%-80%), with a complete response rate of 5% and a partial response rate of 66%; 11% of patients had stable disease. Eight percent of patients had progressive disease, and 9% of patients’ responses were not evaluable (NE).

    The median duration of response (DOR) was 11.0 months (95% CI, 8.5-NE), the disease control rate was 82% (95% CI, 73%-89%), and the median duration of disease control was 10.7 months (95% CI, 7.7-18.8). Additionally, disease control was sustained for at least 52 weeks in 39% of patients, with ongoing responses in 49% of patients at data cutoff with data continuing to mature, said lead study author Martin Wermke, MD, director of Trial Management/Early Clinical Trial Unit, NCT/UCC Early Clinical Trial Unit, of the German Cancer Research Center, University Hospital Carl Gustav Carus Dresden in Dresden, Germany.

    Regarding safety, with a median duration of treatment of 46 weeks (IQR, 14-60), 3 dose limiting toxicities were observed overall, with all patients experiencing treatment-related adverse events (TRAEs) that were grade 3 (43%) or 4 (35%), with 1 patient who died from a TRAE due to sepsis, attributable to the chemotherapy component of the regimen, Wermke said.

    Tarlatamab-related AEs that led to treatment discontinuations occurred in 6% of patients, and immune-related adverse events—not including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and associated neurological events—were reported in 2% of patients.

    The addition of tarlatamab to chemoimmunotherapy demonstrated a manageable safety profile that was consistent with the profiles of each individual agent, explained Wermke.

    “I hope I could convince you that the combination of another frontline chemoimmunotherapy [that is] PD-L1 targeting in the maintenance [setting] is safe and has a manageable toxicity profile,” Wermke said in an oral presentation of the data. “There is no indication of additive or synergistic toxicity.”

    Currently, standard treatment for patients with ES-SCLC comprises chemoimmunotherapy followed by PD-1/PD-L1 treatment as maintenance. Tarlatamab is a bispecific T-cell engager that has been assessed in the second-line setting as a single agent3 in the phase 3 DeLLphi-304 trial (NCT05740566) and in the frontline maintenance setting with a PD-L1 inhibitor in this patient population, as seen in parts 5, 6, and 8 of the phase 1b DeLLphi-303 study.

    At the 2025 ESMO Congress, Wermke presented on safety and efficacy outcomes from parts 2, 4, and 7 from the phase 1b DeLLphi-303 study, which explored tarlatamab in combination with frontline chemoimmunotherapy, followed by tarlatamab with PD-L1 maintenance therapy in patients with ES-SCLC.

    The study enrolled adult patients with ES-SCLC who had received 1 cycle of chemoimmunotherapy, consisting of platinum-etoposide plus an anti-PD-L1 inhibitor, regardless of response to therapy. Patients were also required to have measurable disease via modified RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and no active autoimmune disease or disease that required immunosuppressive therapy. Those with treated and asymptomatic brain metastases were permitted.

    In cycles 1 to 3, patients received tarlatamab at 20 mg intravenously (IV) every 3 weeks plus platinum-etoposide (carboplatin to match area under the curve 5 IV on day 1 and etoposide at 100 mg/m2 on days 1 to 3) and a PD-L1 inhibitor, which consisted of atezolizumab (Tecentriq) at 1200 mg IV every 3 weeks or durvalumab (Imfinzi) at 1500 mg IV every 3 weeks. In the frontline maintenance setting, which was cycles 4 and beyond, patients received tarlatamab at 20 mg IV every 3 weeks plus either of the PD-L1 inhibitors at the aforementioned doses. Treatment was administered until disease progression.

    The coprimary end points were dose-limiting toxicities, treatment-emergent AEs, and TRAEs; secondary end points were ORR, DOR, disease control, progression-free survival (PFS), and overall survival (OS).

    Regarding baseline characteristics, the median age across both arms was 63.0 years (range, 37-86), and 67% of patients were male. Patients were mostly White (74%), followed by Asian (16%), Other (9%), and Black (1%). At diagnosis, 77% had ES disease and 55% had an ECOG performance status of 1. Three-fourths of patients were former smokers, and 67% had prior receipt of a PD-L1 inhibitor in the first standard-of-care cycle; 16% and 45% of patients had treated asymptomatic brain metastases and liver metastases, respectively. The median sum of diameters of target lesions was 82.3 mm (range, 10.0-358.2).

    Wermke noted that the trial was not designed to compare the PD-L1 inhibitors and there were no randomizations between the treatment arms, adding that there were imbalances in baseline characteristics between the atezolizumab and durvalumab groups.

    Further efficacy data showed that the median PFS was 10.3 months (95% CI, 7.2-13.6), starting from the first dose of tarlatamab treatment; the Kaplan-Meier estimate of the 12-month PFS rate was 43.1% (95% CI, 32.0%-53.7%). The median OS is not yet estimable; however, the Kaplan-Meier estimate of the 12-month OS rate with the tarlatamab regimen was 80.6%.

    Investigators also assessed treatment-emergent CRS and ICANS by cycle, which primarily occurred during cycle 1 of tarlatamab (59%) and were mostly of grades 1/2; all CRS/ICANS events resolved. CRS and ICANS events led to both dose interruptions and discontinuations in 1% of patients each, with no fatalities reported. The median time to CRS onset from the last prior tarlatamab dose was 13.3 hours (IQR, 8.0-19.3), and the median time to ICANS onset from the same time point was 5 days (IQR, 3.0-50).

    Wermke concluded that these data support further investigation of this regimen, which will be explored in the phase 3 DeLLphi-312 study (NCT07005128).4

    Disclosures: Wermke cited honoraria from Amgen, BMS GmbH & Co. KG, Boehringer Ingelheim, GWT, Janssen, Lilly, Merck Serono, MJH/PER, Novartis, Pfizer, Regeneron, SYNLAB, and Takeda; consulting or advisory roles for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo Europe GmbH, Genentech, ImCheck Therapeutics, Immatics, Iovance Biotherapeutics, ISA Pharmaceuticals, Lilly, Novartis, PharmaMar, Regeneron, Tacalyx, T-knife, and Zymeworks; receipt of research funding from Roche (paid to the institution); and travel and accommodation expenses from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo Europe GmbH, GEMoaB, Iovance Biotherapeutics, Immatics, Janssen Oncology, Merck Serono, Pfizer, and Sanofi/Aventis.

    References

    1. Wermke M, Lau SCM, Moskovitz M, et al. Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study. Ann Oncol. Abstract 2757O
    2. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Eng J Med. 2025;393:349-361. doi:10.1056/NEJMoa2502099
    3. Paulson KG, Lau SCM, Ahn MJ, et al. Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study. Lancet Oncol. 2025;26(10):1300-1311. doi:10.1016/s1470-2045(25)00480-2
    4. A Study Comparing Tarlatamab, Durvalumab, Carboplatin, and Etoposide Versus Durvalumab, Carboplatin, and Etoposide in First-line Extensive Stage Small-Cell Lung Cancer (ES-SCLC) (DeLLphi-312). ClinicalTrials.gov. Last Updated October 14, 2025. https://tinyurl.com/56ss66yd

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  • NASA supercomputers calculated when life will end on Earth. Here’s our deadline

    NASA supercomputers calculated when life will end on Earth. Here’s our deadline

    In collaboration with researchers from Toho University in Japan, NASA researchers have used supercomputers to model and determine how long life will remain possible on Earth. The calculated end date for all life on Earth is still a long ways…

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  • Kim Seok-hoon’s detox mindset and skincare routine explained

    Kim Seok-hoon’s detox mindset and skincare routine explained

    Kim Seok-hoon leans into candid charm by sharing how a “detox mindset” became the gateway to steadier, brighter skin even under unforgiving studio lights. Framed as lifestyle, not fad, his approach blends onsen getaways, antioxidant habits, and…

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  • Emotional Rune retires from Stockholm SF vs. Humbert – ATP Tour

    1. Emotional Rune retires from Stockholm SF vs. Humbert  ATP Tour
    2. Holger Rune’s Injury: How Long Is He Expected to Be Out of Court After Horrific Scenes in Stockholm?  EssentiallySports
    3. Prayers Pouring In Saturday For Tennis Star Holger Rune  The…

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