- KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain Patients with Muscle-Invasive Bladder Cancer When Given Before and after Surgery UroToday
- Pfizer and Astellas announce positive results from phase 3ev-303 clinical trial for Padcev in combination with Keytruda TradingView
- Enfortumab Vedotin Plus Pembro Cuts Risk of Disease Progression, Death 60% for Patients With MIBC Who Can’t Have Chemo With Bladder Removal The American Journal of Managed Care® (AJMC®)
- ESMO25: Padcev, Keytruda regimen given before, after surgery shines in bladder cancer FirstWord Pharma
- KEYNOTE-905: EV/pembrolizumab emerges as new option for cisplatin-ineligible MIBC Urology Times
Category: 3. Business
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KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain Patients with Muscle-Invasive Bladder Cancer When Given Before and after Surgery – UroToday
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Trump’s Crypto Fortune Soars Amid Policy Shift and Mar
This article first appeared on GuruFocus.
Following the October 11 market correction, risk-off sentiment swept across global crypto markets. Yet, within days, the Trump family’s digital-asset ecosystem including the WLFI platform, the USD1 stablecoin, and American Bitcoin (ABTC) delivered substantial gains. Independent estimates suggest roughly $1.3 billion in new wealth creation, pushing the family’s total net worth to around $7.7 billion. Supporters hail the momentum as a sign of market recovery, while critics warn of regulatory capture and conflicts of interest. The convergence of policy and capital has become a defining feature of this new policy-driven market.
Policy-Capital Feedback Loop:
Since Donald Trump’s inauguration, regulatory posture has softened and pending litigation settlements have accelerated. Liquidity has flowed back into crypto markets, lifting correlated assets tied to the Trump ecosystem.
Two Primary Growth Engines:
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WLFI: Governance-token unlock and institutional accumulation.
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USD1: After the federal compliance framework (Genius Act) took effect, the reserve-based model began generating significant interest income and network expansion.
Industrial Backbone:American Bitcoin (ABTC) went public via merger and Nasdaq listing, seeing sharp intraday volatility and rapid valuation gains.
Core Controversy:The boundary between regulator and regulated remains blurred. The role of offshore capital introduces national-security and governance-integrity concerns.
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Jan 2025: SEC leadership reshuffle ? enforcement pivot.
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Mar Aug 2025: ABTC formed and completed merger with a listed entity.
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Jul 2025: Federal Stablecoin Framework (Genius Act) signed into law.
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Aug 2025: Alt5 Sigma announces $1.5 billion allocation to WLFI.
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Sept 1 2025: WLFI lists publicly ? peak valuation ? $7 billion.
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Sept 3 2025: ABTC debuts on Nasdaq ? intraday valuation ? $13.2 billion.
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WLFI Governance Token: Market debut and institutional buying boosted capitalization and liquidity.
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USD1 Stablecoin: Interest income from reserve assets and ecosystem integration magnified cashflow.
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ABTC Equity Holdings: Public-market repricing increased book value.
Across multiple independent reports, the Trump family’s paper and realized gains for Q3 2025 are estimated around $1.3 billion, with aggregate net worth now near $7.7 billion, including unrealized holdings.
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Policy Reversal: Mid-term politics and regulatory realignment could drive valuation retracement.
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Governance & Ethics: Potential conflicts of interest and offshore funding influence demand greater audit transparency.
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Market Volatility: Post-October 11 secondary sell-offs suggest liquidity recovery remains incomplete.
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Tiragolumab Plus Atezolizumab Fails to Improve Outcomes as Consolidation in NSCLC | Targeted Oncology
Consolidation therapy with tiragolumab plus atezolizumab (Tecentriq) failed to meet the primary end point of improving independent review facility (IRF)-assessed progression-free survival (PFS) vs standard durvalumab (Imfinzi) in patients with locally advanced, unresectable, stage III non–small cell lung cancer (NSCLC) that has not progressed after platinum-based concurrent chemoradiation (cCRT), according to findings from the phase 3 SKYSCRAPER-03 trial presented at the 2025 ESMO Congress.1
At a median follow-up of 30.7 months, the median IRF-PFS in the overall population was 14.2 month (95% CI, 12.6-19.2) in patients receiving the combination vs 13.8 months (95% CI, 10.9-17.0) in patients treated with durvalumab (HR, 1.00; 95% CI, 0.84-1.19). The 24-month PFS event-free rates were 39.0% and 38.5%, respectively. The median overall survival (OS) was 45.6 months (95% CI, 37.1–not evaluable [NE]) vs 45.8 months (95% CI, 36.9-NE), respectively (HR, 0.98; 95% CI, 0.80-1.20). The 24-month OS event-free rates were 67.0% vs 66.3%, respectively.
The primary end point was also missed in PD-L1–positive patients (Tumor Cell [TC] score ≥1%) with a median IRF-PFS of 19.4 months vs 16.6 months in patients treated with the combination vs durvalumab, respectively (HR, 0.96; 95% CI, 0.75-1.23; P = .7586). The median OS in these patients was NE vs 54.8 months, respectively (HR, 0.99; 95% CI, 0.73-1.34). The 24-month PFS and OS event-free survival rates were 46.1% vs 42.9% and 72.2% vs 69.2%, respectively.
“SKYSCRAPER-03 did not meet its primary end point of IRF-PFS. There were no new or unexpected [safety] findings,” said first study author Rafal Dziadziuszko, MD, PhD, department of oncology and radiotherapy of the Medical University of Gdansk, Poland.
What Was the Safety Profile of the Combination and Monotherapy Arms in the SKYSCRAPER-03 trial?
“Tiragolumab plus atezolizumab demonstrated a tolerable safety profile, consistent with previous observations for the combination,” said Dziadziuszko.
Grade 3/4 treatment-related adverse events (TRAEs) occurred in 13.8% of patients in the combination arm, with serious TRAEs experienced by 11.5%. There were 2 patient deaths considered to be related to the combination treatment. In the durvalumab arm, grade 3/4 TRAEs and serious TRAEs each occurred in 10.7% of patients. There were 7 patient deaths considered to be related to durvalumab treatment.
What Was the Study Rationale and Design for the SKYSCRAPER-03 trial?
Regarding the rationale for the study, Dziadziuszko explained, “Consolidation durvalumab is the standard of care for patients with unresectable, stage III NSCLC that has not progressed following cCRT; however, disease recurrence [still] represents an unmet need.”
He added that the immune checkpoint target TIGIT has a role in cancer immune evasion and the study hypothesis was that tiragolumab, an anti-TIGIT monoclonal antibody, could potentially augment antitumor activity when used in combination with immunotherapies such atezolizumab.
The open-label phase 3 SKYSCRAPER-03 trial was launched to test this hypothesis in patients with newly diagnosed, unresectable, stage III NSCLC whose disease has not progressed following at least 2 cycles of definitive platinum-based cCRT. Patients had to have known PD-L1 status, and an ECOG performance status of 0 or 1. Patients with EGFR– or ALK-positive tumors were not eligible for enrollment.
At 1 to 42 days post cCRT, patients were randomized in a 1 to 1 ratio to combination therapy with tiragolumab (840 mg IV every 4 weeks) plus atezolizumab (1680 mg IV every 4 weeks) or single-agent durvalumab (10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks). Patient could receive up to 13 cycles of treatment (28-day cycles).
The primary end point was PFS assessed by an independent review facility in patients with PD-L1–positive (Tumor Cell [TC] score ≥1%) as well as PD-L1 all-comers. Secondary end points included OS, duration of response, objective response rate, patient-reported outcomes, and safety.
What Were the Patient Characteristics in the SKYSCRAPER-03 trial?
Patient characteristics were well balanced between the 2 study arms. The median age was 64 years (range, 35-84) in the combination arm vs 65 years (range, 41-86) in the durvalumab arm. About half of patients in each arm were aged less than 65 years at 50.8% and 47.4%, respectively. About 80% of patients in each arm were male, about 60% were White, and about 35% were Asian. Patients’ ECOG performance status was mostly split evenly between 0 and 1, with a slightly higher number of patients in each arm at ECOG 1 status. About 75% of patients in each arm were former tobacco users and about 20% were current tobacco users.
About 50% of patients in each arm had a PD-L1 TC score of <1%, with about 25% of patients having a score of 1%-49%, and the remaining patients having a score of ≥50%. Tumor staging prior to definitive cCRT showed that 41.1% of patients receiving the combination had stage IIIA tumors vs 39.6% of patients in the single-agent arm. Rates of stage IIIB and stage IIIC tumors were 47.4% vs 44.4% and 11.4% vs 16.0%, respectively. About 60% of patients in each arm had squamous histology and about 40% had non-squamous histology. Best response to concurrent chemoradiotherapy in the combination vs durvalumab arms was complete response (0.5% in each arm), partial response (59.7% vs 61.4%), and stable disease (39.8% vs 38.1%).
In his concluding remarks, Dziadziuszko did not report any next steps for the combination of tiragolumab plus atezolizumab in this setting.
Disclosures
Dziadziuszko disclosed relationships with AstraZeneca, Boehringer Ingelheim, BMS, Pfizer, Takeda, Eli Lilly, BioNTech, Novartis, and Roche.
Reference
1. Dziadziuszko R, Ahn M-J, Bradley JD, et al. SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA69.
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Global AI Competition Could Create Trillion-Dollar Winners
Artificial intelligence (AI) represents a major opportunity for businesses across industries to develop products faster and cheaper than ever before. The race to gain a data-driven edge on the competition is fueling massive investment across the entire tech supply chain from data centers to software.
Many of the key players enabling this new industrial revolution are already valued at over $1 trillion market caps. But as governments and businesses continue to invest in this technology, there are two AI enablers that are still valued under $500 billion that could be worth buying today. Here’s why growing competition in AI could propel these companies into the trillion-dollar club.
Palantir (NASDAQ: PLTR) started as a government contractor, providing AI-powered software for intelligence and counterterrorism efforts. But now its software is experiencing insatiable demand in the private sector. Companies are seeing significant cost savings, which means Palantir can benefit from companies scrambling to adopt AI solutions to remain competitive.
If one company in an industry uses Palantir to gain operating efficiencies, it creates a competitive advantage. This pushes more businesses to consider investing in Palantir’s platforms or risk falling behind. This can explain in part why Palantir’s U.S. commercial revenue has exploded this year, nearly doubling year over year in the second quarter.
Palantir closed its highest quarter yet of total contract-value bookings of $2.3 billion, representing a year-over-year increase of 140%. It is signing bigger deals while also seeing existing customers continue to spend more, leading to a healthy 128% net-dollar retention rate.
Palantir is effectively a tool that improves a company’s profits. Its software is expensive relative to alternative software vendors, but Palantir still expects accelerating growth next quarter. This signals it has a competitive edge. Palantir’s ontology-based system creates a digital twin of a company’s operations, helping managers make sense of unorganized data for better decision making.
Importantly, Palantir is converting revenue into very high margins that are driving robust growth in earnings and free cash flow. This is one reason why the stock has performed so well and may continue to outperform Wall Street’s expectations.
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Chinese Export Boom Can’t Stop Economy’s Slowdown
(Bloomberg) — China’s economy probably grew at the slowest in a year during the third quarter despite a boom in exports, in a disconnect the Communist Party may move to rectify at a key meeting in the coming week.
As trade tensions escalate with the US, weakness in investment, industrial output and retail sales is undermining momentum from record sales abroad. Data due on Monday from China’s National Bureau of Statistics will show gross domestic product rose 4.7% in the quarter from a year earlier, according to the median estimate in a Bloomberg survey, down from 5.2% in the prior three months.
Retail sales are forecast to have expanded 3% in September and industrial output to have climbed by 5% — the weakest outcomes this year for both.
Meanwhile, fixed-asset investment is forecast to have slowed again in the first nine months, to be unchanged from a year earlier. It’s been plunging since May despite a massive expansion in government borrowing meant to support the spending power of local authorities. Public spending on infrastructure hasn’t been enough, though, to make up for a slump in housing investment and the slowdown in money going to manufacturing.
Foreign firms have also been pulling back on outlays, with inbound new foreign direct investment down almost 13% in the first eight months, putting China on track for three straight years of declines. One bright spot is foreign demand, with the goods trade balance so far this year hitting a record $875 billion, according to the latest figures.
The economic fragility sets the tone for the upcoming gathering of party officials at the so-called fourth plenum in Beijing. The huddle will provide clues on their priorities for 2026-2030, as governments and investors around the world call for a rebalancing of China’s economy toward domestic consumption.
What Bloomberg Economics Says:
“Beijing now faces deep structural headwinds — from fading growth drivers to a protracted property downturn and entrenched deflation — unlike the severe, yet temporary pandemic shocks during the last five-year planning stage. With the US ratcheting up trade and tech restrictions, the external environment has also turned sharply adverse. This time, the transition is no longer a distant goal — it’s imperative.”
—Chang Shu, chief Asia economist. For full analysis, click here
The IMF, which just kept its prediction for China’s 2025 growth at 4.8%, expects a slowdown next year to 4.2% — an outlook in line with the median forecasts of economists surveyed by Bloomberg. The fund warned that “China’s prospects remain weak,” saying “real estate investment continues to shrink while the economy teeters on the verge of a debt-deflation cycle.”
“Rebalancing toward household consumption — including through fiscal measures with a greater focus on social spending and the property sector — and scaling back industrial policies would reduce external surpluses and alleviate domestic deflationary pressures,” the IMF officials said in their global economic outlook.
Elsewhere, inflation data from Japan to the UK, purchasing manager indexes from major economies, and the first summary of a meeting by Swiss central bank officials will be among the highlights.
Click here for what happened in the past week, and below is our wrap of what’s coming up in the global economy.
US and Canada
After being delayed by the US government shutdown, the Bureau of Labor Statistics will release of the September consumer price index on Friday. The data, originally slated for Oct. 15, will give Federal Reserve officials a critical piece of information on inflation ahead of their policy meeting the following week.
Economists in a Bloomberg survey forecast the core CPI, which excludes food and fuel for a better snapshot of underlying inflation, to have climbed 0.3% for a third straight month as higher import duties continue to gradually filter through to consumers. The projected monthly gain will keep the annual core CPI at 3.1%.
While most official economic data releases have been delayed, BLS staff were called in despite the shutdown to prepare the September CPI report, which informs next year’s cost-of-living adjustments for Social Security recipients.
Although inflation is stuck above their goal, Fed officials are expected to announce their second rate cut of the year following a two-day meeting on Oct. 28-29 because of the fragile labor market.
Among private-sector economic data on the agenda, a National Association of Realtors report on Thursday will probably show contract closings on purchases of previously owned homes stayed tepid in September. An S&P Global PMI release on Friday is projected to illustrate modest growth in manufacturing and services activity.
For more, read Bloomberg Economics’ full Week Ahead for the US Asia
Apart from the busy week in China, Japan reports national CPI figures on Friday expected to show that consumer inflation remained well above the Bank of Japan’s target in September, while purchasing manager indexes the same day may show manufacturing activity shrinking for a fourth straight month, even as services marked a full year of expansion.
India’s September PMI figures will likely show manufacturing activity remains robust. New Zealand reports quarterly inflation data, while Malaysia, Singapore and Hong Kong release September CPI.
Monthly trade data are due from New Zealand, Thailand and Japan, while South Korea will release 20-day trade statistics for October.
On the policy front, China is likely to hold its 1- and 5-year loan prime rates steady on Monday. Bank Indonesia will mull another cut to its benchmark rate on Wednesday as it weighs benign inflation against the weakening rupiah.
A day later, the Bank of Korea is expected to hold its base rate steady at 2.50% while possibly foreshadowing a cut in November as inflation stays subdued and economic growth cools. Uzbekistan sets rate policy on Thursday.
For more, read Bloomberg Economics’ full Week Ahead for Asia Europe, Middle East, Africa
The week’s highlight may be the initial reading of October purchasing manager indexes across western Europe.
These will reveal how manufacturing and services companies in Germany, France and the UK assessed the activity at the start of the fourth quarter, pointing to any momentum — or lack thereof — at a time when President Donald Trump’s tariffs are squeezing exports to the US.
In terms of hard data, Britain may draw the most attention. Public finance numbers on Tuesday will inform Chancellor Rachel Reeves as she prepares for a fraught budget in November.
Inflation the following day will be crucial both for Reeve’s plans and the Bank of England, which is inching toward further rate cuts while nervously monitoring still-strong price pressures. The data are likely to show acceleration to 4%, the fastest in 1 1/2 years.
In the euro zone, several European Central Bank speakers will deliver remarks before a pre-decision quiet period kicks in on Thursday. Among them will be Executive Board members Isabel Schnabel and Philip Lane on Monday, and President Christine Lagarde on Wednesday.
Meanwhile, France’s ongoing struggles to pass a budget are likely to continue after Prime Minister Sebastien Lecornu survived two no-confidence votes in the past week. Political strife could yet force the collapse of his government.
The situtation was exacerbated by Friday night’s unscheduled move by S&P Global Ratings to downgrade the country. The move means France has lost its double-A rating at two of the three major credit assessors in little more than a month, potentially forcing some funds with ultra-strict investment criteria to sell the country’s bonds.
An update at Moody’s Ratings is due at the end of the coming week, though the firm currently has a stable outlook on the country.
Belgium is also on the calendar for a possible review from S&P Global Ratings, whose view on its credit score is already skewed negative.
In Switzerland on Tuesday, September export numbers will offer a glimpse into the country’s trade position at the end of a quarter when it got slapped with the highest US import tariffs of any advanced economy. The government cited those levies in cutting its growth forecast for next year.
Thursday will be a watershed moment for the Swiss National Bank with the release of its first-ever summary of a rate meeting discussion, in an attempt to emulate the sort of transparency practiced by the Fed.
Turning south, data on Wednesday will likely show South African inflation ticked up to 3.4% in September from 3.3%. That may again persuade policymakers to hold rates steady for a second consecutive meeting next month as they defend the South African Reserve Bank’s stricter 3% goal for price growth, which they signaled in July is their preferred level.
A day later, the central bank will publish its semi-annual monetary policy review and Governor Lesetja Kganyago will offer more insights.
For more, read Bloomberg Economics’ full Week Ahead for EMEA Some monetary decisions are scheduled around the region:
On Tuesday, the National Bank of Hungary is set to keep its rate on hold at 6.5%, having rebuffed government calls for easing. Turkey’s central bank is likely to lower rates again on Thursday — by 100 basis points to 39.5%, according to a Bloomberg survey. Still, some in the poll expect a hold after price growth unexpectedly picked up in September to 33.3% year-on-year. The Bank of Russia will announce its latest rate decision on Friday, after cuts at the past three meetings brought the benchmark to 17%. Governor Elvira Nabiullina has warned that the widening federal budget deficit, driven by spending on the war in Ukraine, may limit room for further cuts. Latin America
In a light week, Mexico may face a second straight month of negative GDP-proxy prints for August, due largely to more restricted public spending and Trump’s trade policies.
In similar vein, August data from Argentina may show activity extending a slump as President Javier Milei’s shock therapy weighs on the economy.
Also due from Argentina is Torcuato Di Tella University’s government confidence index, which is fresh off a tumble and may have taken another leg down amid a sell-off of the peso and local assets. Much is riding on how Milei fares in the Oct. 26 midterm elections.
Providing regional contrast material, Colombia’s August GDP-proxy report comes on the heels of July data that showed growth got off to a blistering start in the second half, in line with central bank forecasts.
Mid-month inflation reports from Brazil and Mexico are likely to show still-simmering price pressures.
Sticky and elevated core readings are likely to keep Brazil’s central bank on hold at 15% into 2026, though readings in Mexico are very unlikely to see Banxico pause its easing cycle after 10 straight rate cuts.
For more, read Bloomberg Economics’ full Week Ahead for Latin America –With assistance from Brian Fowler, Laura Dhillon Kane, Vince Golle, Monique Vanek, Robert Jameson, Mark Evans, Tony Halpin, Paul Abelsky and Paul Wallace.
©2025 Bloomberg L.P.
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Chinese Export Boom Can’t Stop Economy’s Slowdown
An Antong Holdings Co. container ship at the Port of Nansha in Guangzhou, China.
(Bloomberg) — China’s economy probably grew at the slowest in a year during the third quarter despite a boom in exports, in a disconnect the Communist Party may move to rectify at a key meeting in the coming week.
Most Read from Bloomberg
As trade tensions escalate with the US, weakness in investment, industrial output and retail sales is undermining momentum from record sales abroad. Data due on Monday from China’s National Bureau of Statistics will show gross domestic product rose 4.7% in the quarter from a year earlier, according to the median estimate in a Bloomberg survey, down from 5.2% in the prior three months.
Retail sales are forecast to have expanded 3% in September and industrial output to have climbed by 5% — the weakest outcomes this year for both.
Meanwhile, fixed-asset investment is forecast to have slowed again in the first nine months, to be unchanged from a year earlier. It’s been plunging since May despite a massive expansion in government borrowing meant to support the spending power of local authorities. Public spending on infrastructure hasn’t been enough, though, to make up for a slump in housing investment and the slowdown in money going to manufacturing.
Foreign firms have also been pulling back on outlays, with inbound new foreign direct investment down almost 13% in the first eight months, putting China on track for three straight years of declines. One bright spot is foreign demand, with the goods trade balance so far this year hitting a record $875 billion, according to the latest figures.
The economic fragility sets the tone for the upcoming gathering of party officials at the so-called fourth plenum in Beijing. The huddle will provide clues on their priorities for 2026-2030, as governments and investors around the world call for a rebalancing of China’s economy toward domestic consumption.
What Bloomberg Economics Says:
“Beijing now faces deep structural headwinds — from fading growth drivers to a protracted property downturn and entrenched deflation — unlike the severe, yet temporary pandemic shocks during the last five-year planning stage. With the US ratcheting up trade and tech restrictions, the external environment has also turned sharply adverse. This time, the transition is no longer a distant goal — it’s imperative.”
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T-DXd Superior to T-DM1 in Improving IDFS/DFS in Residual HER2+ Breast Cancer | Targeted Oncology
Interim data from the phase 3 DESTINY-Breast05 trial (NCT04622319) shared at the 2025 European Society for Medical Oncology (ESMO) Congress showed improved invasive disease–free survival (IDFS) with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) gin compared with ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with high-risk, HER2-positive primary breast cancer with residual invasive disease following neoadjuvant therapy.1
Treatment with T-DXd (n = 818) led to a 53% reduction in the risk of invasive disease or death compared with T-DM1 (n = 817; HR, 0.47; 95% CI, 0.34–0.66; P < .0001). The 3-year IDFS rates were 92.4% (95% CI, 89.7%–94.4%) with T-DXd vs 83.7% (95% CI, 80.2%–86.7%) with T-DM1.
“Patients benefited [from T-DXd] irrespective of age cohorts, region of accrual, hormone receptor status, disease status at presentation, post-therapy pathologic nodal status, and dual or single HER2-targeted therapy, as well as irrespective of the sequence or usage of radiation therapy for that minority of patients who did not receive [radiation] treatment,” Charles E. Geyer Jr., MD, said in the presentation.
Geyer is a professor of medicine and chief of the Division of Malignant Hematology and Medical Oncology at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania.
What Was the Rationale for DESTINY-Breast05?
Previously, the phase 3 KATHERINE trial (NCT01772472 ) showed that T-DM1 improved IDFS (HR, 0.50; 95% CI, 0.39-0.64; P < .0001) and overall survival (OS; HR, 0.66; 95% CI, 0.51-0.87; P = .0027) compared with trastuzumab in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy.2 However, patients with advanced locoregional disease or positive nodal status following neoadjuvant therapy had 3-year IDFS rates of 76% and 83%, respectively; the 7-year IDFS rates were 67% and 72%, respectively.1 These data reinforce the unmet need for improved post-neoadjuvant treatment in this population, Geyer emphasized.
What Was the Study Design?
This global, multicenter, randomized, open-label trial enrolled patients with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant chemotherapy with a HER2-directed therapy. Patients needed to present with high-risk disease prior to neoadjuvant therapy, defined as inoperable early breast cancer or operable early breast cancer with axillary node–positive disease after neoadjuvant therapy. Patients also needed to have centrally confirmed HER2-positive disease and an ECOG performance status of 0 or 1. Enrolled patients were stratified by extent of disease at presentation (inoperable vs operable), type of HER2-targeted neoadjuvant therapy received (single vs dual), hormone receptor status (positive vs negative), and post-neoadjuvant therapy pathologic nodal status (positive vs negative).
Patients were randomly assigned 1:1 to receive intravenous (IV) T-DXd at 5.4 mg/kg every 3 weeks for 14 cycles, or IV T-DM1 at 3.6 mg/kg every 3 weeks for 14 cycles. Treatment was followed by a 40-day safety follow-up period.
Notably, concomitant adjuvant endocrine therapy was allowed per local practice protocols. Additionally, radiotherapy, if administered, could be initiated concurrently with study therapy or completed prior to the initiation of study therapy per the investigator. An interstitial lung disease (ILD) monitoring program was required for patients who received radiotherapy.
IDFS served as the primary end point, with disease-free survival (DFS) as a key secondary end point. Other secondary end points included OS, distant recurrence–free interval (DRFI), brain metastasis–free interval (BMFI), and safety.
What Did the Patient Population Look Like?
In total, 1635 patients were randomly assigned to receive T-DXd (n = 818) or T-DM1 (n = 817). In the T-DXd arm, 806 patients received treatment. A total of 27.7% of patients in this arm discontinued treatment due to adverse effects (AEs; 17.9%), patient withdrawal (7.4%), disease recurrence (0.2%), physician decision (1.9%), and protocol deviation (0.2%). In total, 72.3% of patients in this arm completed study treatment, and the median study duration was 29.9 months (range, 0.3-53.4).
In the T-DM1 arm, 801 patients received treatment. A total of 23.7% of patients in this arm discontinued treatment due to AEs (12.7%), patient withdrawal (6.2%), disease recurrence (3.7%), physician decision (0.6%), protocol deviation (0.1%), and other reasons (0.1%). In total, 76.3% of patients in this arm completed study treatment, and the median study duration was 29.7 months (range, 0.1-54.4).
In the T-DXd arm, the median age was 50.3 years (range, 24–78), Asian patients were the most predominant race (48.8%), and most patients had HER2 3+ disease by immunohistochemistry (IHC) (82.6%), hormone receptor–positive disease (71.0%), inoperable disease (52.7%), positive nodal status (80.7%), received dual HER2-targeted therapy with trastuzumab plus pertuzumab (77.9%), prior anthracycline use (51.7%), and received prior adjuvant radiotherapy (93.4%). In the T-DM1 arm, the median age was 50.6 years (range, 21-83), Asian patients were the most predominant race (47.2%), and the highest proportions of patients had HER2 3+ disease by IHC (82.0%), hormone receptor–positive disease (71.4%), inoperable disease (51.9%), positive nodal status (80.5%), received dual HER2-targeted therapy with trastuzumab plus pertuzumab (78.5%), prior anthracycline use (48.8%), and received prior adjuvant radiotherapy (92.9%).
What Additional Efficacy Outcomes Were Observed?
Overall, investigators observed lower rates of distant and local recurrences, including central nervous system (CNS) recurrences, with T-DXd vs T-DM1. The numbers of patients with recurrences in these respective arms were as follows:
- Distant recurrence: n = 42 (non-CNS, n = 25; CNS, n = 17); n = 77 (non-CNS, n = 52; CNS, n = 25)
- Local invasive recurrence: n = 1; n = 5
- Regional recurrence: n = 1; n = 6
- Contralateral invasive disease: n = 0; n = 6
- Death without prior reported event: n = 7; n = 8
A DFS benefit was observed with T-DXd vs T-DM1 (HR, 0.47; 95% CI, 0.34–0.66; P < .0001). The 3-year DFS rates were 92.3% (95% CI, 89.5%–94.3%) with T-DXd vs 83.5% (95% CI, 79.9%–86.4%) with T-DM1.
DRFI, BMFI, and OS benefits were also seen with T-DXd vs T-DM1. The respective 3-year DRFI rates were 93.9% (95% CI, 91.4%–95.7%) and 86.1% (95% CI, 82.5%–89.1%); the HR was 0.49 (95% CI, 0.34–0.71) favoring the T-DXd arm. The respective 3-year BMFI rates were 97.6% (95% CI, 96.2%–98.5%) and 95.1% (95% CI, 93.6%–97.2%); the HR was 0.64 (95% CI, 0.35–1.17) favoring the T-DXd arm. The respective 3-year OS rates were 97.4% (95% CI, 95.8%–98.4%) and 95.7% (95% CI, 93.5%–97.2%); the HR was 0.61 (95% CI, 0.34–1.10) favoring the T-DXd arm.
Regarding on-study treatment exposure, in the T-DXd arm, the median study treatment duration was 9.8 months, and 72.3% of patients completed the planned 14 cycles of therapy. In the T-DM1 arm, the median study treatment duration was 9.7 months, and 76.3% of patients completed the planned 14 cycles of therapy. Notably, patients who discontinued the study before receiving 14 cycles of study treatment were permitted to receive an additional HER2-targeted therapy per standard of care (SOC) guidelines to complete 14 total cycles of HER2-targeted adjuvant therapy.
What Was the Safety Profile?
In the T-DXd arm, any-grade treatment-emergent AEs (TEAEs) were reported in 99.5% of patients, and 50.6% of patients experienced grade 3 or higher TEAEs. Serious TEAEs (17.4%) and those associated with drug discontinuation (17.9%; drug-related ILD/pneumonitis, 10.8%), drug interruptions (49.6%), dose reductions (26.4%), and deaths (0.4%; ILD/pneumonitis, n = 2; respiratory tract infection adjudicated as not ILD, n = 1) also occurred.
In the T-DM1 arm, any-grade TEAEs were reported in 98.4% of patients, and 51.9% of patients experienced grade 3 or higher TEAEs. Serious TEAEs (13.6%) and those associated with drug discontinuation (12.9%; drug-related ILD/pneumonitis, 2.5%), drug interruptions (41.1%), dose reductions (26.6%), and deaths (0.6%; leiomyosarcoma of the uterus, aneurysm, non-neutropenic sepsis, ovarian cancer, and traumatic pneumothorax, n = 1 each) also occurred.
The most commonly reported TEAEs in the T-DXd and T-DM1 arms, respectively, were nausea (71.3%; 29.3%), constipation (32.0%; 16.2%), decreased neutrophil counts (31.6%; 14.4%), vomiting (31.0%; 9.0%), decreased white blood cell counts (29.7%; 13.0%), fatigue (29.5%; 20.2%), radiation pneumonitis (28.8%; 27.0%), anemia (28.3%; 17.0%), increased aspartate aminotransferase levels (25.6%; 50.2%), increased alanine aminotransferase levels (23.7%; 45.3%), diarrhea (23.2%; 8.6%), decreased platelet counts (21.2%; 49.8%), decreased appetite (20.0%; 10.0%), headache (15.8%; 20.7%), and arthralgia (10.3%; 20.5%).
The rates of adjudicated drug-related ILD in the T-DXd and T-DM1 arms were as follows:
- Any-grade: 9.6% vs 1.6%
- Grade 1: 2.0% vs 1.0%
- Grade 2: 6.5% vs 0.6%
- Grade 3: 0.9% vs 0%
- Grade 4: 0% vs 0%
- Grade 5: 0.2% vs 0%
No differences in adjudicated drug-related ILD instances were observed based on adjuvant radiotherapy timing (sequential or concurrent). Investigators observed similar distributions of any-grade adjudicated drug-related ILD events with sequential (T-DXd arm, 10.7%; T-DM1 arm, 2.6%) and concurrent (9.6%; 1.0%) radiotherapy.
The rates of left ventricular dysfunction in the T-DXd and T-DM1 arms were as follows:
- Any-grade: 2.9% vs 1.7%
- Grade 1: 0.1% vs 0%
- Grade 2: 2.5% vs 1.4%
- Grade 3: 0.2% vs 0.4%
- Grade 4: 0% vs 0%
- Grade 5: 0% vs 0%
“Adjuvant T-DXd demonstrated superior efficacy with manageable safety in patients with high-risk, HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy, which represents a potential new SOC in this post-neoadjuvant setting,” Geyer concluded.
DISCLOSURES: Geyer reported receiving grants from or having contracts with Daiichi Sankyo, AstraZeneca, Roche/Genentech, and Exact Sciences; receiving meeting and/or travel support from Exact Sciences; receiving honoraria or travel expenses from Exact Sciences and Merck; and receiving support for the current presentation from Daiichi Sankyo and AstraZeneca.
REFERENCES:
1. Geyer CE, Park YH, Shao Z, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): interim analysis of DESTINY-Breast05. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA1.
2. Kadcyla. Prescribing information. Genentech; revised May 2025. Accessed October 18, 2025. https://www.gene.com/download/pdf/kadcyla_prescribing.pdf
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Invikafusp Alfa Boasts High Disease Control Rate in Checkpoint Inhibitor–Resistant Solid Tumors
Invikafusp alfa led to tumor regression in target lesions in 52% of patients with tumor mutational burden–high (TMB-H) or microsatellite instability–high (MSI-H) solid tumors resistant to immune checkpoint blockade, according to data from the phase 2 START-001 trial (NCT05592626) presented at the
2025 ESMO Congress .1Across the 4 biomarker-enriched populations with TMB-H tumors, TMB-H gastrointestinal cancers, TMB-H metastatic colorectal cancer (mCRC), and MSI-H tumors, the objective response rates (ORRs) were 20.5% (n = 9 of 44), 27.8% (n = 5 of 18), 33.3% (n = 3 of 9), and 30% (n = 3 of 10), respectively. The respective disease control rates were 79.5% (n = 35 of 44), 77.8% (n = 14 of 18), 66.7% (n = 6 of 9), and 70% (n = 7 of 10). Notably, the TMB-H cohort included patients with CRC, gastric, lung, breast, and other cancers.
“Invikafusp alfa, a first-in-class bispecific dual T-cell agonist, demonstrated clinically meaningful monotherapy activity in heavily pretreated immune checkpoint blockade–resistant/insensitive tumors harboring high tumor mutations,” presenting study author Antoine Italiano, MD, PhD, professor of medicine, head of Early Phase Trials Unit at the Institut Bergonié, and head of Precision Medicine at Gustave Roussy in France, stated in the presentation.
What Was the Study Rationale?
Immunotherapy resistance poses a clinical challenge as it limits the number of effective treatment options that are available to patients. Tumor-infiltrating lymphocyte therapies have shown promise in the immuno-oncology (IO)–refractory setting, with Vβ6/10 T-cell subsets representing the most common subset.
Invikafusp alfa was designed to selectively activate and expand Vβ10 T-cell subsets to overcome resistance to immune checkpoint blockade.
What Were the Enrollment Criteria?
Eligibility criteria required that patients have unresectable, locally advanced or metastatic, TMB-H, MSI-H, or virally-associated solid tumors in phase 1, and TMB-H, MSI-H/mismatch repair–deficient (dMMR) tumors, including TMB-H and/or MSI-H CRC in phase 2.2 An ECOG performance status of 0 or 1 was required in both phases. Prior treatment with PD-(L)1 inhibition was allowed. In phase 2, patients with hepatic metastases were not permitted unless they had been treated and were stable.
Phase 1 followed a traditional dose-escalation design in which patients received either 0.01 mg/kg, 0.02 mg/kg, 0.04 mg/kg, 0.08 mg/kg, 0.12 mg/kg, or 0.16 mg/kg of invikafusp alfa.1 The dose expansion phase was broken into 3 cohorts: TMB-H (n = 56; cohort 1), MSI-H/dMMR (n = 29), and TMB-H and/or MSI-H/dMMR mCRC (n = 23 to 56). In phase 2, all patients received the recommended phase 2 dose (RP2D) of 0.08 mg/kg of the agent intravenously every 2 weeks.
The primary objective of phase 1 was to determine the RP2D and evaluate the safety and tolerability of the regimen. ORR per immune RECIST criteria served as the primary objective of phase 2.
What Patient Characteristics Were Presented?
As of July 9, 2025, 55 patients with TMB-H/MSI-H tumors had been enrolled in phase 2, adding to the 8 that had been enrolled in phase 1 at the optimal biologic dose. Represented tumor types (n = 63) included CRC (25.4%), non–small cell lung cancer (14.3%), head and neck squamous cell carcinoma (7.9%), gastric cancer (6.3%), breast cancer (4.8%), cutaneous cancer (4.8%), endometrial cancer (4.8%), melanoma (4.8%), anal cancer (3.2%), basal cell carcinoma (3.2%), gastroesophageal junction cancer (3.2%), pancreatic cancer (3.2%), bladder cancer (1.6%), cervical cancer (1.6%), duodenal adenocarcinoma (1.6%), esophageal cancer (1.6%), neuroendocrine carcinoma cells (1.6%), ovarian cancer (1.6%), prostate cancer (1.6%), thymic cancer (1.6%), and thyroid cancer (1.6%).
The median age was 61 (range, 53-69) and most patients were male (95.2%), White (63.5%), and had an ECOG performance status of 1 (52.8%). Most patients received between 1 and 3 prior lines of therapy (65.1%), prior treatment with an immune checkpoint inhibitor (67%), and had TMB-H disease (73.0%). Best response to prior immunotherapy was largely split between partial response (30.1%), stable disease (16.7%), progressive disease (26.2%), and unknown (26.2%).
Was the Agent’s Mechanism of Action Indicative of Its Safety Profile?
Italiano noted that the safety profile was consistent with the agent’s mechanism of action. The most common treatment-related adverse effects (TRAEs) were cytokine release syndrome (grade 1, 22.2%; grade 2, 46.0%; grade 3, 12.7%), rash (grade 1, 11.1%; grade 2, 34.9%; grade 3, 7.9%), nausea (grade 1, 28.6%; grade 2, 20.6%; grade 3, 1.6%), pruritus (grade 1, 22.2%; grade 2, 20.6%; grade 3, 6.3%), vomiting (grade 1, 17.5%; grade 2, 31.7%; grade 3, 0%), alanine aminotransferase increase (grade 1, 22.2%; grade 2, 4.8%; grade 3, 9.5%), platelet count decrease (grade 1, 11.1%; grade 2, 12.7%; grade 3, 12.7%), chills (grade 1, 15.9%; grade 2, 11.1%; grade 3, 0%), diarrhea (grade 1, 19.0%; grade 2, 6.3%; grade 3, 1.6%), peripheral edema (grade 1, 9.5%; grade 2, 7.9%; grade 3, 0%), and increased blood bilirubin (grade 1, 7.9%; grade 2, 4.8%; grade 3, 3.2%).
“No step-up dosing and no immune checkpoint inhibitor–type immune-related adverse effects were reported. TRAEs were on target and well managed with supportive care, including corticosteroids such as tocilizumab (Actemra),” Italiano said.
What Are the Key Takeaways From This Presentation?
“Selective activation of the T-cell Vβ repertoire represents a novel class of IO bispecific therapy, with broad potential as a next generation T-cell–targeted multi-specific antibody platform for the advancement of precision immunotherapy,” Italiano concluded.
Disclosures: No disclosures were presented for Italiano.
References
- Garralda E, Italiano A, Marabelle A, et al. START-001: initial phase 2 clinical activity of invikafusp alfa, a first-in-class T cell receptor (TCR) β-chain-targeted bispecific antibody as monotherapy in patients with antigen-rich solid tumors resistant to immune checkpoint blockade (ICB). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA55.
- A study of a selective T cell receptor (TCR) targeting, bifunctional antibody-fusion molecule STAR0602 in participants with advanced solid tumors (START-001). Clinicaltrials.gov. Updated July 9, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT05592626
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Evaluating Valuation After Ignite AI Advisor Launch and Major Industry Changes
Equifax (EFX) has rolled out its new Ignite AI Advisor platform, which brings lender-focused analytics and generative AI capabilities to the forefront. This launch comes at a time of industry shifts, including changes to credit scoring access that could affect future revenue.
See our latest analysis for Equifax.
Despite Equifax’s ongoing push into AI-powered products for lenders, the company’s recent developments arrive amid shifting industry dynamics and competitive pressures. Over the past year, shareholders have faced a total return decline of nearly 19%, while the share price has fallen almost 10% year-to-date. This serves as a reminder that sentiment has faded even as management pursues new growth avenues. Meanwhile, three- and five-year total shareholder returns remain solidly positive, suggesting longer-term investors have still come out ahead.
If you’re interested in uncovering what else is gaining momentum beyond the headlines, this is a great time to expand your search and discover fast growing stocks with high insider ownership
Given recent innovations and ongoing industry disruptions, the key question for investors is whether Equifax’s current valuation still leaves room for upside, or if the market is already pricing in the company’s growth prospects.
Equifax’s most widely followed fair value narrative puts the company’s worth at $277.70 per share, notably above the last close price of $226.91. This suggests that, according to current consensus, the market is not yet pricing in all the drivers that underpin the long-term outlook.
“Accelerating customer adoption of new multi-data product solutions (e.g., TWN indicator, Single Data Fabric, EFX.AI) and continued high NPI (New Product Introduction) rates are expanding Equifax’s value proposition and positioning the company to capture incremental market share and drive sustained organic revenue growth above historical levels. Structural expansion of government verification requirements (e.g., semiannual redeterminations, added work requirements, improper payment focus) and a rising TAM for eligibility verification services are set to benefit long-term revenue growth and reduce business cyclicality as Equifax’s solutions become more critical to federal and state programs.”
Read the complete narrative.
Curious what’s behind that premium price? The secret sauce is in the projected pace of revenue expansion, ambitious margin targets, and a future earnings multiple seldom seen in the industry. Want to see which bullish financial levers drive this fair value? Click through for the complete playbook; your next big insight could be one number away.
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Tarlatamab Improves OS vs Chemotherapy in SCLC, Regardless of Prior PD-(L)1 Therapy or CFI Duration
Tarlatamab-dlle (Imdelltra) demonstrated a significant overall survival (OS) advantage over standard chemotherapy in patients with small cell lung cancer (SCLC), irrespective of chemotherapy-free interval (CFI) duration or prior anti–PD-(L)1 therapy, according to results from the phase 3 DeLLphi-304 trial (NCT05740566) presented at the
2025 ESMO Congress .The median OS was 10.9 months in the tarlatamab arm vs 6.4 months in the chemotherapy arm among patients with a CFI of less than 90 days (HR, 0.60; 95% CI, 0.43-0.84). The 12-month OS rates in this population were 40% vs 24% with tarlatamab and chemotherapy, respectively.
Among patients with a CFI of 90 days or longer, the median OS was 17.1 months compared with 10.6 months in each arm, with respective 12-month OS rates of 64% and 48% (HR, 0.65; 95% CI, 0.45-0.93). Regarding patients with disease progression within 2 weeks of their most recent platinum-containing treatment, the Kaplan-Meier estimated 6-month OS rates were 55% with tarlatamab and 35% with chemotherapy.
Among patients with prior receipt of anti–PD-(L)1 agents, the median OS was 14.1 months in the tarlatamab arm and 8.3 months in the chemotherapy arm; the respective 12-month OS rates were 53% vs 36% (HR, 0.61; 95% CI, 0.45-0.82). In the group of patients without prior anti–PD-(L)1 therapy, the median OS was 13.6 months vs 8.3 months, and the 12-month OS rates were 53% vs 40% (HR, 0.65; 95% CI, 0.42-1.03). Overall, data showed that prior exposure to anti–PD-(L)1 agents did not affect OS benefits with tarlatamab vs chemotherapy.
“In the second line, standard chemotherapies have demonstrated modest survival benefits, especially [in] those patients with platinum-resistant disease, [who] often have a poor prognosis. DeLLphi-304 is the first randomized phase 3 trial to demonstrate superior OS with tarlatamab compared with standard chemotherapy. Importantly, this survival benefit extended to patients with platinum-resistant disease,” presenting author Pedro F. Simoes da Rocha, MD, PhD, of Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology in Barcelona, Spain, stated in the presentation.1 “These findings reinforce the use of tarlatamab as a standard of care in second-line SCLC, including those patients with worse prognosis, such as [those] with platinum-resistant disease.”
In the randomized DeLLphi-304 trial, 509 patients were assigned 1:1 to receive tarlatamab (n = 254) or investigator’s choice of chemotherapy (n = 255), which included options of topotecan (n = 185), lurbinectedin (Zepzelca; n = 47), and amrubicin (n = 23). Investigators stratified patients by prior receipt of anti–PD-(L)1 agents, CFI interval, presence of brain metastases, and intended chemotherapy.
The trial’s primary end point was OS. Secondary end points included progression-free survival, patient-reported outcomes, objective response rate, and safety.
Patients with histologically or cytologically confirmed SCLC, disease progression following frontline platinum-based chemotherapy with or without anti–PD-(L)1 therapy, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Those with asymptomatic, treated, or untreated brain metastases were able to enroll.
In the tarlatamab and chemotherapy arms, respectively, 43% and 45% of patients had a CFI of less than 90 days, and 57% and 55% had a CFI of 90 days or longer. Additionally, 71% of patients in both arms had prior receipt of anti–PD-(L)1 therapy, while 29% from both arms did not. Investigators noted that subgroup baseline characteristics appeared to be balanced between treatment arms.
Across the different CFI and anti–PD-(L)1 subgroups, rates of grade 3 or higher treatment-related adverse effects (AEs) ranged from 24% to 30% in the tarlatamab arm and 58% to 69% in the chemotherapy arm. Any-grade events of cytokine release syndrome (CRS) occurred in 51% to 59% of patients who received tarlatamab across various subgroups, and subgroup status did not impact the risk of CRS.
Previously, the
FDA granted accelerated approval to tarlatamab as a treatment for patients with extensive-stage SCLC following progression on prior platinum-based chemotherapy in May 2024.2 Supporting data for this indication came from the phase 2 DELLphi-301 trial (NCT05060016).References
- Rocha P, Sun L, Cho BC, et al. Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase 3 DeLLphi-304 trial. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. LBA101.
- FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed October 18, 2024. https://tinyurl.com/48k34rw5
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