Onco-Summaries: Daily Oncology Updates at a Glance
25/09/2026
In Phase 3 EXCALIBER-RRMM trial, ZENBEXUS™-based therapy significantly improved response depth and MRD-negative CR versus DVd in RRMM ()
Bristol Myers Squibb reported first time results from the prespecified analysis of Phase 3 EXCALIBER-RRMM trial evaluating ZENBEXUS™ (iberdomide; CELMoD agent) in combination with Johnson & Johnson's daratumumab (anti-CD38) and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM).
The study demonstrated significantly deeper responses compared with daratumumab, bortezomib, and dexamethasone (DVd), supporting the potential of iberdomide as a new treatment option in earlier relapse settings
The primary endpoint of MRD-negative complete response (CR) was achieved, with ZDd (iberdomide + daratumumab + dexamethasone) demonstrating a significantly higher MRD-negative CR rate than Dvd (daratumumab + bortezomib + dexamethasone)
Analysis included 420 evaluable patients with a median follow-up of 15.7 months
Endpoint | ZDd | DVd |
MRD-negative Complete Response (Primary Endpoint) | 41.1% | 20.7% |
p<0.0001 | ||
Overall Response Rate (ORR) | 88.9% | 76.1% |
Complete Response or Better | 45.9% | 24.9% |
Grade 3/4 Neutropenia | 84.3% | 11.3% |
Grade 3/4 Infections | 39.2% | 21.6% |
Any-Grade Peripheral Neuropathy | 12.3% | 42.6% |
Grade 3/4 Peripheral Neuropathy | 2.9% | 5.4% |
Clinical benefit was observed across key subgroups, including lenalidomide-exposed and lenalidomide-refractory patients
The progression-free survival analysis, a co-primary endpoint, remains ongoing
Based on EXCALIBER-RRMM results, ZENBEXUS received FDA accelerated approval on August 13, 2026 for adults with multiple myeloma who have received at least one prior line of therapy including both a proteasome inhibitor and an immunomodulatory agent
The results position iberdomide-based therapy as a potential new backbone regimen in first-relapse multiple myeloma, particularly for patients previously treated with or refractory to lenalidomide, with differentiated efficacy and reduced neuropathy relative to a bortezomib-based standard of care
In Phase 2 CARTITUDE-2 study, single CARVYKTI infusion delivered 5-year treatment-free remission in 50% of early-line RRMM patients (Ref)
Johnson & Johnson reported long-term follow-up data from Cohort A of the Phase 2 CARTITUDE-2 study evaluating CARVYKTI® (ciltacabtagene autoleucel; BCMA-directed autologous CAR-T cell therapy) in patients with early-line relapsed/refractory multiple myeloma (RRMM)
The update highlights the durability of response achieved with a single CAR-T infusion and provides further evidence supporting earlier use of CARVYKTI in the treatment paradigm
Parameter | Result |
Median Follow-up | 60.7 months |
5-Year Progression-Free Survival (PFS) | 50% |
Patients Alive & Progression-Free at 5 Years | 10/20 (50%) |
Median PFS | 60.5 months |
5-Year Overall Survival (OS) | 69.2% |
Maintenance Therapy | None required among patients remaining progression-free at 5 years |
MRD Status at 5 Years | 3/3 evaluable patients MRD-negative (10⁻⁶ sensitivity) |
High-Risk Cytogenetics | 50% of 5-year progression-free patients had ≥1 high-risk cytogenetic abnormality |
Safety | No new CAR-T-related neurotoxicity signals; safety profile remained consistent with prior reports |
US FDA granted priority review for imfinzi + enfortumab vedotin in cisplatin-ineligible MIBC (Ref)
AstraZeneca announced that the U.S. FDA has granted Priority Review to perioperative Imfinzi (durvalumab; anti-PD-L1) plus neoadjuvant Astellas Pharma & Pfizer's Padcev (enfortumab vedotin; nectin-4 targeted ADC) for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or decline cisplatin-based chemotherapy
The regulatory submission is supported by results from the Phase III VOLGA trial, with an FDA decision expected in Q4 2026
Regulatory applications are currently under review in the EU, Japan and several other countries
The Phase III VOLGA trial demonstrated statistically significant and clinically meaningful improvements in both event-free survival (EFS) and overall survival (OS) compared with the control arm.
The safety profile was consistent with the known profiles of the individual agents, with no new safety signals identified.
The study enrolled 695 patients across 182 centers in 25 countries, evaluating perioperative durvalumab plus neoadjuvant enfortumab vedotin, with or without tremelimumab.
Approximately half of MIBC patients are unable to receive cisplatin-based chemotherapy, highlighting a significant unmet need in this population
MSD and Daiichi Sankyo have voluntarily withdrawn the US BLA for I-DXd in previously treated ES-SCLC (Ref)
Merck & Co / MSD and Daiichi Sankyo announced the voluntary withdrawal of the U.S. Biologics License Application (BLA) for Ifinatamab Deruxtecan (I-DXd; B7-H3-directed ADC) in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC), following discussions with the FDA regarding the adequacy of the current data package for accelerated approval
The FDA concluded that the available clinical evidence, including data from the Phase 2 IDeate-Lung01 study, does not currently support accelerated approval in this indication.
Development of I-DXd in SCLC continues, with enrollment nearing completion in the Phase 3 IDeate-Lung02 trial evaluating I-DXd versus physician's choice chemotherapy in relapsed ES-SCLC after one prior platinum-based regimen.
The companies indicated that future regulatory submissions may be pursued based on results from the Phase 3 study
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