Qaasid News

Download Our App

Category: 3. Business

  • Trodelvy® Reduces Risk of Disease Progression or Death by 38% Versus Chemotherapy as First-Line Therapy in Patients With Metastatic Triple-Negative Breast Cancer in ASCENT-03 Study

    – Late-Breaking ASCENT-03 Data Simultaneously Presented at ESMO 2025 and Published in The New England Journal of Medicine –

    – With Two Positive Phase 3 Trials, Trodelvy Has Potential as the First and Only ADC to be a Backbone Standard of Care for All First-Line Metastatic TNBC Patients Regardless of PD-L1 Status –

    FOSTER CITY, Calif.–(BUSINESS WIRE)–
    Gilead Sciences, Inc. (Nasdaq: GILD) today shared positive data from the Phase 3 ASCENT-03 study demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) for Trodelvy® (sacituzumab govitecan-hziy) compared to chemotherapy as first-line treatment in patients with metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitors. These findings will be presented today during a late-breaking oral session at the 2025 European Society for Medical Oncology (ESMO) Congress (Abstract #LBA20) and simultaneously published in The New England Journal of Medicine.

    ASCENT-03 successfully met its primary endpoint of PFS with a 38% reduced risk of disease progression or death for Trodelvy versus chemotherapy (HR: 0.62; p<0.0001). Median PFS with Trodelvy was 9.7 months versus 6.9 months for chemotherapy. The PFS results for Trodelvy versus chemotherapy were consistent across prespecified subgroups, including among patients with poorer prognosis (such as those whose cancer recurred less than one year after treatment in the curative setting) and regardless of chemotherapy chosen.

    “Patients with metastatic TNBC who are ineligible for immunotherapy face an especially poor prognosis, with limited treatment options and fast disease progression,” said Dr. Javier Cortés, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. “The ability of sacituzumab govitecan to significantly delay death and progression could represent the first major treatment advance for this patient population in the 20 years since TNBC was defined, marking an historic shift and establishing a potential new standard of care.”

    The objective response rate (ORR) was 48% with Trodelvy and 46% with chemotherapy. Median duration of response (DOR) was substantially longer with Trodelvy. Among patients with confirmed complete or partial responses, DOR for Trodelvy was 12.2 months compared to 7.2 months with chemotherapy.

    Overall survival (OS) data were not mature at the time of PFS primary analysis. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned.

    These results complement the recent presentation of ASCENT-04/KEYNOTE-D19, which showed a significant PFS benefit for Trodelvy plus Keytruda® (pembrolizumab) in PD-L1+ first-line metastatic TNBC. Gilead is engaging with the U.S. Food and Drug Administration and other global regulators regarding both data sets.

    “ASCENT-03 is the second Phase 3 trial with a Trodelvy-based regimen to show superior progression-free survival over chemotherapy in first-line metastatic TNBC, highlighting its potential to improve outcomes for patients with limited treatment options,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “With these potentially practice-changing results, Trodelvy is poised to transform the first-line metastatic TNBC treatment landscape, offering a much-needed alternative to chemotherapy.”

    Summary of Key ASCENT-03 Results

    Efficacy: Intent-to-Treat Population

    Trodelvy (n=279)

    Chemotherapy (n=279)

    Median PFS

    9.7 months (95% CI: 8.1-11.1)

    6.9 months (95% CI: 5.6-8.2)

    PFS hazard ratio and p-value

    0.62 (95% CI: 0.50-0.77); p<0.0001

    ORR

    48% (95% CI: 42-54)

    46% (95% CI: 40-52)

    DOR

    12.2 months (95% CI: 9.7-13.8)

    7.2 months (95% CI: 5.7-8.4)

    The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. The most frequent grade ≥3 treatment-emergent adverse events were neutropenia (43%) and diarrhea (9%) with Trodelvy and neutropenia (41%) and anemia (16%) with chemotherapy. Fewer patients discontinued treatment due to adverse events on Trodelvy than with chemotherapy (4% vs. 12%).

    Healthcare professionals have well-established experience with Trodelvy, with more than 60,000 breast cancer patients treated across 50+ countries over the past five years. It remains the only Trop-2-directed antibody-drug conjugate (ADC) to demonstrate meaningful survival benefits in both 2L+ metastatic TNBC and pre-treated HR+/HER2- metastatic breast cancer. It is also the only ADC with four positive Phase 3 trials in HER2- mBC (IHC 0, IHC 1+, or IHC 2+/ISH–).

    The use of Trodelvy plus Keytruda in patients with first-line PD-L1+ metastatic TNBC and Trodelvy as monotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors are investigational, and the safety and efficacy of these uses have not been established.

    KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

    About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors)

    Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

    Chemotherapy remains the mainstay of treatment in first-line metastatic TNBC patients who are not candidates for PD-1/PD-L1 inhibitors, and the need to improve outcomes continues to be high as there has not been a clinically meaningful advance for this patient population in over 20 years. In metastatic TNBC overall, ~50% of patients do not receive treatment beyond the first-line setting, demonstrating a need for additional effective earlier-line treatment options.

    About the ASCENT-03 Study

    The ASCENT-03 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of Trodelvy compared with treatment of physician’s choice in patients with previously untreated, locally advanced, inoperable, or metastatic triple-negative breast cancer whose tumors do not express PD-L1, or who are PD-L1 positive and previously treated with a PD-(L)1 inhibitor in the curative setting. 558 patients were enrolled across multiple study sites worldwide.

    Patients were randomized 1:1 to receive either Trodelvy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were eligible to cross over to Trodelvy upon disease progression.

    The primary endpoint of the study is progression-free survival (PFS) as assessed by BICR according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs) and safety.

    More information about ASCENT-03 is available at ClinicalTrials.gov: NCT05382299.

    About Trodelvy

    Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

    Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

    Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

    INDICATIONS

    TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

    • Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
    • Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

    IMPORTANT SAFETY INFORMATION

    BOXED WARNING: NEUTROPENIA AND DIARRHEA

    • TRODELVY can cause severe, life-threatening, or fatal neutropenia. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Primary prophylaxis with G-CSF is recommended for all patients at increased risk of febrile neutropenia. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
    • TRODELVY can cause severe diarrhea. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.

    CONTRAINDICATIONS

    • Severe hypersensitivity reaction to TRODELVY.

    WARNINGS AND PRECAUTIONS

    Neutropenia: Severe, life-threatening, or fatal neutropenia can occur as early as the first cycle of treatment and may require dose modification. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities. Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 of USPI.

    Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

    Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause serious hypersensitivity reactions including life-threatening anaphylactic reactions. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue TRODELVY for Grade 4 infusion-related reactions.

    Nausea and Vomiting: TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

    Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

    Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

    ADVERSE REACTIONS

    In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).

    In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

    In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes.

    DRUG INTERACTIONS

    UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

    UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY.

    Please see full Prescribing Information, including BOXED WARNING.

    About Gilead and Kite Oncology

    Gilead and Kite Oncology are working to transform how cancer is treated. We are innovating with next-generation therapies, combinations and technologies to deliver improved outcomes for people with cancer. We are purposefully building our oncology portfolio and pipeline to address the greatest gaps in care. From antibody-drug conjugate technologies and small molecules to cell therapy-based approaches, we are creating new possibilities for people with cancer.

    About Gilead Sciences

    Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. In 2025, Gilead announced a planned $32 billion investment to further strengthen its U.S. footprint to power the next era of discovery, job creation and public health preparedness – while continuing to invest globally to ensure patients everywhere benefit from its scientific innovation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif.

    Forward-Looking Statements

    This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Trodelvy (such as ASCENT-03); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for programs and/or indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements.

    Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.

    U.S. Prescribing Information for Trodelvy, including BOXED WARNING, is available at www.gilead.com.

    For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).


    Source: Gilead Sciences, Inc.

    Continue Reading

  • ESMO: Tubulis’ next-gen ADC posts 59% response rate, justifying investor interest – Fierce Biotech

    1. ESMO: Tubulis’ next-gen ADC posts 59% response rate, justifying investor interest  Fierce Biotech
    2. German biotech firm Tubulis raises $358 million to develop targeted cancer treatments  MSN
    3. Tubulis lands record 308 million euro funding to advance ADC pipeline  The Pharma Letter
    4. Wellington Management Joins $361M Series C for Cancer Drug Developer Tubulis  citybiz
    5. Research transfer: LMU spin-off Tubulis secures financing for cancer research  LMU München

    Continue Reading

  • FLAURA2 Trial: Osimertinib Plus Chemotherapy Improves Overall Survival Across Prognostic Subgroups in EGFR-Mutated Advanced NSCLC — Presented at ESMO 2025

    FLAURA2 Trial: Osimertinib Plus Chemotherapy Improves Overall Survival Across Prognostic Subgroups in EGFR-Mutated Advanced NSCLC — Presented at ESMO 2025

    The Phase 3 FLAURA2 trial (NCT04035486) continues to strengthen the role of combination therapy in the first-line management of EGFR-mutated (EGFRm) advanced non–small cell lung cancer (NSCLC). At ESMO 2025, investigators reported the final overall survival (OS) analysis, showing that osimertinib (osi) plus platinum–pemetrexed chemotherapy (CTx) achieved a statistically significant and clinically meaningful OS improvement compared with osimertinib monotherapy.

    This milestone confirms the combination as a first-line standard of care in EGFRm NSCLC, offering durable efficacy across key subgroups, including those with traditionally poor prognostic features such as CNS metastases, L858R mutations, plasma-detectable EGFRm, and altered TP53.

    Methods

    The FLAURA2 trial enrolled 557 patients with EGFRm advanced NSCLC, who were randomized 1:1 to receive osimertinib plus chemotherapy (n=279) or osimertinib alone (n=278). The chemotherapy regimen consisted of platinum–pemetrexed, administered concurrently with osimertinib.

    Baseline CNS imaging (CT or MRI) was mandatory to identify central nervous system metastases. EGFR mutation subtypes (Ex19del or L858R) were confirmed through central or locally approved assays. Plasma EGFR mutation detection was evaluated via droplet digital PCR (Biodesix), while TP53 mutation status was determined using FoundationOne CDx.

    OS outcomes were analyzed using an unstratified Cox proportional hazards model, with subgroup analyses conducted based on baseline prognostic factors.

    Results

    A total of 557 patients were included: 279 in the osimertinib + CTx arm and 278 in the osimertinib monotherapy arm. The overall hazard ratio (HR) for OS was 0.77 (95% CI 0.61–0.96; p=0.02), corresponding to a 23% reduction in risk of death with the combination regimen.

    CNS Metastases

    In patients with baseline CNS metastases, median OS reached 40.9 months (95% CI 35.2–46.6) with osimertinib + CTx versus 29.7 months (95% CI 25.6–35.8) with monotherapy (HR 0.72; 95% CI 0.52–0.99).

    EGFR Mutation Subtype

    Both EGFRm subgroups derived benefit.

    • L858R: median OS 38.1 vs 32.4 months (HR 0.76; 95% CI 0.55–1.07)
    • Ex19del: median OS not reached (NR) vs 43.0 months (HR 0.76; 95% CI 0.56–1.02)

    Plasma EGFR Mutation Detection

    Patients with detectable plasma EGFRm achieved median OS 38.4 vs 32.5 months (HR 0.79; 95% CI 0.60–1.03), while those with undetectable mutations had not reached median OS in either arm.

    TP53 Alteration Status

    Among patients with altered TP53, OS improved to 51.1 months vs 43.1 months (HR 0.71; 95% CI 0.40–1.27), showing consistent benefit across molecular profiles.

    No new safety signals were reported, confirming that the addition of chemotherapy did not compromise the established tolerability of osimertinib.

    flaura2-trial

    Interpretation

    The survival improvement observed with osimertinib plus chemotherapy extended across every prognostic subgroup examined. The HRs for OS within each category closely mirrored those of the overall intent-to-treat (ITT) population, highlighting the robustness and reproducibility of the benefit.

    Particularly noteworthy were the gains among patients with CNS metastases and L858R mutation, two subsets traditionally associated with poorer prognosis. These data underline the capacity of the combination regimen to overcome key resistance mechanisms and delay disease progression.

    flaura2-trial

    Long-Term Follow-Up and Analytical Considerations

    The long-term follow-up from the FLAURA2 trial at ESMO 2025 provides the most comprehensive survival dataset to date for EGFR-mutated NSCLC treated with first-line osimertinib plus chemotherapy. With several subgroups not yet reaching median OS, the sustained separation of survival curves indicates a persistent and cumulative treatment effect extending well beyond the chemotherapy phase.

    Investigators emphasized that the survival curves for osimertinib + CTx began to diverge early—within the first year of treatment—and remained separated throughout follow-up, suggesting that early dual blockade of EGFR signaling and microenvironmental suppression via chemotherapy offers durable control of micrometastatic disease.

    The analysis also highlights that median OS was not reached in multiple subgroups, demonstrating an ongoing trend toward improved long-term outcomes. The consistency of benefit across genomic and clinical subgroups—including those with TP53 alterations or detectable circulating tumor DNA—supports the biological rationale that concurrent chemotherapy may help prevent the emergence of resistant clones.

    Methodologically, the trial’s unstratified Cox model ensured unbiased subgroup comparisons and confirmed that the treatment effect was independent of baseline risk characteristics. Furthermore, despite crossover and subsequent therapies available post-progression, the OS advantage with osimertinib plus chemotherapy persisted, reinforcing the value of front-line combination therapy over sequential monotherapy strategies.

    No late-emerging toxicities or cumulative safety concerns were identified during long-term follow-up, strengthening the safety profile of the regimen. Together, these findings establish osimertinib plus chemotherapy as a durable, well-tolerated, and biologically rational first-line standard of care for patients with EGFR-mutated advanced NSCLC.

     

    Read Full Abstract on ESMO Congress 2025 Website 

    You Can Watch More on OncoDaily Youtube TV

    Written by Armen Gevorgyan, MD

    Continue Reading

  • EV + Pembrolizumab Boosts Survival in MIBC

    EV + Pembrolizumab Boosts Survival in MIBC

    KEYNOTE-905/EV-303 (NCT03924895), a phase 3, open-label, randomized trial, evaluated perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) compared with surgery alone in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or declined cisplatin-based chemotherapy.

    Presented by Prof. Christof Vulsteke at the ESMO Congress 2025, the study demonstrated that adding EV + pembro to radical cystectomy with pelvic lymph node dissection resulted in significant improvements in event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR). These findings mark a major advance for cisplatin-ineligible MIBC, establishing a potential new perioperative standard of care.

    Background

    Radical cystectomy with pelvic lymph node dissection (RC + PLND) remains the standard of care for patients with muscle-invasive bladder cancer. However, nearly half of these patients are ineligible for cisplatin-based chemotherapy due to renal dysfunction, frailty, or comorbidities, leaving a substantial population without effective perioperative options.

    Previous studies have shown limited benefit from surgery alone in this setting, underscoring the unmet need for alternative strategies. Enfortumab vedotin, an antibody–drug conjugate targeting Nectin-4, combined with pembrolizumab, has demonstrated potent antitumor activity and a favorable safety profile in metastatic urothelial cancer, providing a strong rationale for evaluation in the perioperative context.

    Methods

    KEYNOTE-905/EV-303 is a randomized, open-label, phase 3 trial that enrolled adults with MIBC (T2–T4aN0M0 or T1–T4aN1M0) who were cisplatin-ineligible per Galsky criteria or declined cisplatin.
    Participants were randomized 1:1 to receive:

    • EV + pembro arm: Three cycles of EV (1.25 mg/kg on days 1 and 8) plus pembrolizumab (200 mg every three weeks) before RC + PLND, followed by six additional EV cycles and 14 cycles of pembrolizumab postoperatively.
    • Control arm: RC + PLND alone, with adjuvant nivolumab permitted when clinically indicated.

    The primary endpoint was event-free survival (EFS) by blinded independent central review (BICR).Key secondary endpoints included overall survival (OS), pathologic complete response (pCR), and safety.

    Timeline of study development:

    • The study initiated in 2019 with two treatment arms—perioperative pembrolizumab + RC + PLND vs RC + PLND alone—randomized 1:1.
    • In 2020, a third arm was added, introducing perioperative EV + pembro + RC + PLND, changing the randomization to 1:1:1.
    • By 2022, the design evolved: the pembrolizumab-alone arm was discontinued, and randomization was updated to 1:1 between EV + pembro + RC + PLND (EV + pembro arm) and RC + PLND (control arm).
    • The inclusion criteria were expanded to include patients who were cisplatin-eligible but declined cisplatin, broadening the real-world relevance of the study population.
    • Adjuvant nivolumab was permitted in the control arm per local guidelines.

    Results

    A total of 344 participants were randomized between December 2020 and June 2024 (170 to EV + pembro; 174 to control). Over 80% were cisplatin-ineligible, and the median follow-up was 25.6 months (range 11.8–53.7).The combination regimen produced statistically significant and clinically meaningful improvements across all efficacy endpoints:

    • Event-Free Survival (EFS): Median EFS was not reached with EV + pembro versus 15.7 months with control (HR 0.40; 95% CI 0.28–0.57; P<0.0001). At one years, EFS rates were 77.8% vs 55.1%, respectively and at two years, 74,7% vs 39,4%

    KEYNOTE-905/EV-303 trial

    • Overall Survival (OS): Median OS was not reached with EV + pembro versus 41.7 months with control (HR 0.50; 95% CI 0.33–0.74; P=0.0002). The 12-month OS rates were 86.3% vs 75.7%, and the 24-months OS rates were 79,7% vs 63,1%

    KEYNOTE-905/EV-303 trial

    • Pathologic Complete Response (pCR): 57.1% with EV + pembro vs 8.6% with control, an absolute difference of 48.3% (95% CI 39.5–56.5; P<0.0001).

    KEYNOTE-905/EV-303 trial

     

    Safety:

    Treatment-emergent adverse events (TEAEs) occurred in nearly all patients (100% in EV + pembro vs 64.8% in control). Grade ≥3 events were reported in 71.3% and 45.9%, respectively. The most frequent grade ≥3 adverse events of special interest were severe skin reactions (11.4%) related to pembrolizumab and cutaneous toxicity (10.8%) associated with enfortumab vedotin.

    Despite the high incidence of AEs, the safety profile remained manageable and consistent with prior studies, and no new safety signals were identified.

    Conclusions

    The KEYNOTE-905/EV-303 trial demonstrated that adding perioperative enfortumab vedotin plus pembrolizumab to standard surgery significantly improved event-free survival, overall survival, and pathologic complete response rates in patients with cisplatin-ineligible MIBC.

    These findings establish EV + pembrolizumab as the first perioperative regimen to improve outcomes versus RC + PLND alone in this population, offering a potential new standard of care.

     

    You can read the full abstract here.

    Continue Reading

  • “On the Fence About Buying Drone Companies that Aren’t Making Money”

    “On the Fence About Buying Drone Companies that Aren’t Making Money”

    Red Cat Holdings, Inc. (NASDAQ:RCAT) is one of the stocks Jim Cramer was focused on recently. When a caller asked about the stock during the lightning round, Cramer said:

    “Okay, so this is a Ben Stoto favorite, not really. It’s a drone company. We are on the fence about buying drone companies that aren’t making money.”

    Pixabay/Public Domain

    Red Cat Holdings, Inc. (NASDAQ:RCAT) develops drone systems and control technologies for military, government, and commercial use. During the February 18 episode, Cramer mentioned the stock and remarked:

    “This one just happens to be a personal favorite of our chief scientist, Ben Stoto. We talk about Red Cat a lot. It’s a data analytics company, and you know what? I’m going to tell you, you can buy it. You really can. Because if it doubled, you’d feel like an idiot for not buying Red Cat.”

    It is worth noting that since the above comment was made, the company’s stock gained around 65%.

    While we acknowledge the potential of RCAT as an investment, we believe certain AI stocks offer greater upside potential and carry less downside risk. If you’re looking for an extremely undervalued AI stock that also stands to benefit significantly from Trump-era tariffs and the onshoring trend, see our free report on the best short-term AI stock.

    READ NEXT: 30 Stocks That Should Double in 3 Years and 11 Hidden AI Stocks to Buy Right Now.

    Disclosure: None. This article is originally published at Insider Monkey.

    Continue Reading

  • Assessing Futu Holdings (NasdaqGM:FUTU) Valuation After a 100% Year-to-Date Share Price Surge

    Assessing Futu Holdings (NasdaqGM:FUTU) Valuation After a 100% Year-to-Date Share Price Surge

    Futu Holdings (NasdaqGM:FUTU) shares have seen a steady climb this year, with the stock up over 100% year-to-date. Many investors are now reviewing its recent performance and growth numbers for insights into what might come next.

    See our latest analysis for Futu Holdings.

    Futu Holdings has enjoyed sustained momentum, with a 105.8% year-to-date share price return. This reflects renewed investor confidence and optimism around its growth story. Over the past year, its total shareholder return reached 79.4%, underscoring long-term performance beyond just recent gains.

    If you’re weighing what else might be showing breakout momentum, this is a great moment to broaden your search and discover fast growing stocks with high insider ownership

    With shares surging so impressively, the central question becomes whether Futu Holdings is still undervalued at current levels, or if the market is already accounting for the company’s future growth potential and leaving little room for upside.

    Compared to Futu Holdings’ last close price of $163.53, the most widely followed narrative estimates a fair value of $207.27. The picture that emerges is of a company with catalysts that some see as transformative, and a valuation that challenges the market’s current view.

    The rapid growth in funded accounts, especially from international markets such as Singapore, the U.S., Malaysia, and Japan, signals ongoing global expansion and diversification of Futu’s user base. This positions the company to capture rising middle-class wealth and digital financial adoption in Asia, supporting long-term revenue and AUM growth.

    Read the complete narrative.

    What is driving that bold upside call? This narrative is built on expectations of relentless customer growth, a resilient business model, and margin strength usually reserved for industry leaders. The surprising mix of ambitious projections and global expansion creates a valuation thesis you will not want to miss.

    Result: Fair Value of $207.27 (UNDERVALUED)

    Have a read of the narrative in full and understand what’s behind the forecasts.

    However, risks remain, as heightened competition in key Asian markets and regulatory hurdles could quickly turn investor optimism into caution for Futu Holdings.

    Find out about the key risks to this Futu Holdings narrative.

    While many focus on analyst price targets, compare Futu Holdings’ current price-to-earnings ratio of 22.4x against the industry average of 25.4x and a peer average of 22.2x. However, the fair ratio for Futu is estimated at 21.4x, suggesting that shares could be slightly expensive. This is an important detail for those weighing potential returns or risks.

    See what the numbers say about this price — find out in our valuation breakdown.

    NasdaqGM:FUTU PE Ratio as at Oct 2025

    If the narrative above doesn’t reflect your perspective, why not take a closer look at the figures yourself and craft your own in just a few minutes using Do it your way

    A good starting point is our analysis highlighting 3 key rewards investors are optimistic about regarding Futu Holdings.

    Don’t let great opportunities pass you by. Expand your watchlist with high-potential stocks you may have missed. Use these targeted screens to stay one step ahead:

    This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

    Companies discussed in this article include FUTU.

    Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com

    Continue Reading

  • A US-China trade dispute over a little-known Dutch chipmaker could bring auto plants to a halt and send car prices higher

    A US-China trade dispute over a little-known Dutch chipmaker could bring auto plants to a halt and send car prices higher

    Few car buyers have heard of Nexperia. But this Dutch company makes chips that are essential for making cars — and now, it’s at the center of a trade dispute that could shutter global auto plants and send already-record-level car prices even higher.

    The dispute is just one part of wider trade tensions between the United States and China. The Nexperia saga began in earnest this past December when the US Commerce Department put Nexperia’s parent company, China-based Wingtech Technologies, on a list of companies facing trade restrictions.

    Then, this October, China’s Ministry of Commerce banned Nexperia China and its subcontractors from exporting specific finished components and sub-assemblies manufactured in China. The Dutch government took control of Nexperia following this move.

    The tensions have prompted concerns of possible auto plant shutdowns, since the chips Nexperia makes are critical to the assembly of the cars and trucks in which they’re installed. The fear is that the trade dispute could halt Nexperia’s production of the chips, and it would be difficult to replace them.

    When and if auto plants might be forced to halt operations is not clear. But a similar chip shortage following the pandemic caused temporary plant shutdowns and the supply of new autos to drop significantly for more than a year. That shortage in turn helped drive up the price of both new and used cars.

    Vehicles have become more dependent on computer chips, transistors and diodes on everything from adjusting driver’s seats to feeding the proper amount of fuel into engines and providing braking power. Vehicles can’t be completed if those critical components are unavailable.

    While Nexperia is little known outside the industry, its site says the company has more than 6,000 products qualified for use in automobiles, and shipments of 110 billion of its products annually. It has 12,500 employees across Europe, Asia and the United States. It said it’s working on business continuity plans and is “confident that a solution will be found.”

    But automaker trade groups are less confident and have sounded the alarm of possible auto plant shutdowns.

    “If the shipment of automotive chips doesn’t resume – quickly – it’s going to disrupt auto production in the U.S. and many other countries and have a spillover effect in other industries,” John Bozzella, CEO of the Alliance for Automotive Innovation, a lobbying group for most major automakers, said in a statement. “It’s that significant. We’re urging a quick resolution, so U.S. and global automaking remains on track.”

    The European Automobile Manufacturers Association said it would take months to get new supplies of the components its members have been getting from Nexperia, while the supply of its chips is expected to last only weeks.

    “Automakers have taken steps over the last years to diversify supply chains but risk cannot be mitigated down to zero. This is a cross-industry issue affecting a large number of suppliers and virtually all of our members,” Sigrid de Vries, director general of the European associations, said in a statement.

    “We suddenly find ourselves in this alarming situation,” she added. We really need quick and pragmatic solutions from all countries involved.”

    Nexperia make about 40% of the automotive chips in the segment of the market that includes transistors and diodes, according to Ian Riches, vice president of the global automotive practice for research firm TechInsights.

    Automakers are already being forced to deal with increased costs due to tariffs being imposed by the Trump administration. While many are absorbing the costs so far, Kelley Blue Book came out with an estimate last week that the average US new car price just topped $50,000 for the first time.

    Continue Reading

  • ADC Improves Outcomes for Patients with Advanced Triple-Negative Breast Cancer Who are Ineligible for Immune Checkpoint Inhibitors

    Patients with an aggressive form of breast cancer who are not candidates for immune checkpoint inhibitor therapy showed significantly improved progression-free survival when treated with the antibody drug conjugate sacituzumab govitecan compared to standard chemotherapy. These findings, which stem from the ASCENT-03 trial in triple-negative breast cancer co-led by investigators at Dana-Farber Cancer Institute, are presented today at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. They are also published simultaneously in the New England Journal of Medicine.

    Triple-negative breast cancer (TNBC) accounts for about 15% of all breast cancer cases and is often difficult to treat. The 5-year survival rate for patients with metastatic disease is about 15%. Moreover, around 60% of patients with metastatic TNBC have tumors that lack the molecular marker PD-L1. This absence indicates the tumors will not respond to immune checkpoint inhibitors. For most patients with previously untreated TNBC, chemotherapy is the primary treatment option.

    “There are limited treatment options for patients with advanced triple-negative breast cancer — and that is especially true for those patients whose tumors are PD-L1-negative,” says Dr. Sara Tolaney, chief of the Division of Breast Oncology at Dana-Farber and senior author on the study. “Finding novel treatments that are effective in this patient population is a major priority for the field.”

    Sacituzumab govitecan, an antibody drug conjugate (ADC), targets the protein Trop2, which is present at high levels on the surfaces of TNBC cells. The ADC binds to Trop2 and, through its molecular payload, delivers a potent chemotherapy drug directly to tumor sites. Sacituzumab govitecan is currently approved as a second-line treatment for patients with advanced TNBC. However, roughly half of patients with this disease do not go on to receive a second line of therapy, underscoring the magnitude of the unmet need.

    ASCENT-03, a global, randomized, open-label phase 3 study, evaluates the use of sacituzumab govitecan versus standard chemotherapy as a first-line treatment in patients with locally advanced or unresectable TNBC who are not candidates for immune checkpoint inhibitors. A total of 558 patients across 229 clinical sites in 30 countries were enrolled and randomized to receive either sacituzumab govitecan or chemotherapy. In both treatment groups, about 99% of patients had PD-L1 negative tumors (277 out of 279 for sacituzumab govitecan; 278 out of 279 for chemotherapy).

    After a median follow-up of 13.2 months, patients treated with sacituzumab govitecan were more likely to survive longer without disease progression, with a median progression-free survival of 9.7 months compared to 6.9 months for patients treated with chemotherapy. Those who responded showed a median duration of response of 12.2 months, compared to 7.2 months for those patients who responded to chemotherapy.

    Data on overall survival are immature at this time. The safety profile of sacituzimab govitecan was consistent with its known profile and was manageable with current guidelines and supportive care.

    “As oncologists and investigators, we’re always trying to move more effective therapies into earlier lines of treatment because we want patients to be able to have robust responses that potentially will translate into survival outcomes,” says Tolaney. “The data from ASCENT-03 are very compelling and support sacituzumab govitecan as a potential new standard of care for patients with previously untreated triple-negative breast cancer who are unable to receive immune checkpoint inhibitors.”

    Dana-Farber investigators were involved in the first studies of sacituzumab govitecan in humans and participated in the pivotal clinical trials that led to its initial U.S. Food and Drug Administration approval for patients with pre-treated triple-negative breast cancer. Tolaney also helped lead the TROPiCS-02 study, which led to the ADC’s approval in pre-treated patients with HR-positive, HER2-negative metastatic breast cancer. Earlier this year, Dr. Tolaney presented results of the phase 3 ASCENT-04/KEYNOTE-D19 trial, which showed the combination of sacituzumab govitecan plus pembrolizumab resulted in durable responses with improved progression free survival compared to current standard treatment in patients with metastatic triple negative breast cancer that tests positive for the immune checkpoint PD-L1.

    Funding: The ASCENT-03 trial was funded by Gilead Sciences, Inc.

    Continue Reading

  • Drug groups unveil advances in treating most difficult breast cancers

    Drug groups unveil advances in treating most difficult breast cancers

    Stay informed with free updates

    AstraZeneca, Daiichi Sankyo and Gilead have made big advances in treating the hardest-to-tackle type of breast cancer, boosting prospects for tens of thousands of patients a year.

    The drugmakers are unveiling trial results for existing blockbuster drugs in “triple negative” breast cancer — so-called because it is not one of the three main types. These include the first ever study showing a medicine can extend the life of patients who cannot be treated with immunotherapy drugs, the majority of triple negative cases.

    Patients with triple negative breast cancer make up about 10 per cent to 20 per cent of people diagnosed. Breast cancer is the most common type of the disease in the UK, and the second most common after skin cancer in the US.

    AstraZeneca and Japanese pharma company Daiichi’s drug Datroway improved overall survival for patients by 23 per cent, and increased the time they lived without the cancer getting worse by 43 per cent, compared with those treated with chemotherapy.

    David Frederickson, executive vice-president for oncology at AstraZeneca, said the results showed an “outstanding opportunity” to expand treatment to more patients. The company has had 10 positive late-stage trial results in oncology this year, five of which have been in breast cancer.

    “It’s been an exceptional year,” he said. “The breast cancer studies alone have the opportunity to reach nearly half a million patients.”

    Frederickson added AstraZeneca’s oncology sales rose 16 per cent year-on-year in the first half and he hopes they will contribute half of the company’s goal of $80bn of sales by 2030.

    AstraZeneca and Daiichi also announced positive trial results for their Enhertu breast cancer drug in earlier-stage patients. The treatment is approved for later-stage patients but it is not available on the NHS in England, even though it is in many other countries including Scotland.

    One of two Enhertu studies found a three-year disease-free survival rate of 92 per cent, compared with 84 per cent with the most commonly used drugs.

    Fredrickson said there needs to be a “modernisation” of NHS methodologies, including valuing the end of life more, to ensure patients can get access.

    The results were presented at the European Society for Medical Oncology this weekend, where US drugmaker Gilead also reported positive results for its cancer drug Trodelvy in patients with triple negative breast cancer.

    Trodelvy, which is already approved for breast cancer, reduced the risk of cancer progression or death by 38 per cent versus other forms of chemotherapy. Survival rates were extended with the drug to 9.7 months versus 6.9 months for chemotherapy, the company said.

    Trodelvy generated $657mn for Gilead in the first six months of 2025, up 5 per cent from the same period last year. Oncology accounts for about 12 per cent of the company’s sales.

    The latest data for Trodelvy marks a bounceback for the drug. A year ago, Gilead withdrew it for certain urinary tract cancers after it failed a drug trial.

    Eli Lilly also reported encouraging data. Its Verzenio drug prolonged survival for certain high-risk early breast cancers by 15.8 per cent versus conventional treatments. It is the first therapy in more than two decades to demonstrate a significant overall survival benefit in certain, high-risk early breast cancers.

    Continue Reading

  • Air China flight safely diverted to Shanghai after battery fire in cabin

    Air China flight safely diverted to Shanghai after battery fire in cabin

    Representative image
    | Photo Credit: Getty Images/iStockphoto

    A commercial passenger flight operated by Air China was safely diverted to Shanghai on Saturday (October 19, 2025) after a battery stowed in a passenger’s carry-on luggage caught fire, the airline said.

    The incident occurred aboard the national carrier’s daily flight from the eastern Chinese city of Hangzhou to Incheon International Airport, near Seoul, South Korea.

    “A lithium battery spontaneously ignited in a passenger’s carry-on luggage stored in the overhead bin on flight CA139,” the airline said in a statement on Chinese social media platform Weibo.

    “The crew immediately handled the situation according to procedures, and no one was injured,” the statement said.

    The plane was diverted for an unscheduled landing at Shanghai Pudong International Airport “to ensure flight safety”, it added.

    Bright flames were seen coming from an overhead storage compartment in an image taken by a passenger and published by state-affiliated domestic media outlet Jimu News.

    There was black smoke in the cabin, the image showed, as at least one passenger was seen trying to extinguish the blaze.

    Data from tracking website Flightradar24 showed that the flight took off from Hangzhou at 9:47 a.m. local time.

    It made a complete turn over the sea roughly equidistant from the eastern Chinese coast and Japan’s southern island of Kyushu, landing in Shanghai shortly after 11am local time.

    Published – October 19, 2025 11:47 am IST

    Continue Reading