Ivonescimab extended median overall survival to 30.8 months versus 22.6 months for pembrolizumab in first-line treatment of PD-L1-positive (TPS ≥1%) advanced non-small cell lung cancer, cutting the risk of death by 27%. Data presented by Caicun Zhou of Shanghai East Hospital at the 2024 WCLC make ivonescimab the first drug to beat pembrolizumab head-to-head in a phase 3 trial with positive results on both progression-free and overall survival.
Iberdomide plus daratumumab and dexamethasone significantly improved MRD-negative complete response versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma in the phase 3 EXCALIBER-RRMM trial. The most common grade 3 or 4 adverse events were haematological events and infections, mostly manageable with standard supportive care. The findings support this combination as an efficacious option across diverse care settings.
Half of multiple myeloma patients in Cohort A of the Phase 2 CARTITUDE-2 study remained alive and progression-free after a single dose of Carvykti, with a median follow-up of 60.7 months. Of 20 patients treated after one to three prior lines of therapy, 10 were alive without progression, and overall survival at this timepoint was 69.2%. The data extend evidence for the BCMA-targeting CAR T therapy in earlier-line use, where Gilead's anito-cel awaits an FDA decision on Dec. 23.
A single infusion of CARVYKTI (cilta-cel) kept 10 of 20 patients (50%) with relapsed/refractory multiple myeloma alive and progression-free at five years without maintenance therapy. The CARTITUDE-2 cohort A data, with a median follow-up of 60.7 months, cover patients who had received 1 to 3 prior lines of therapy. The results extend the durability evidence for cilta-cel into earlier-line RRMM.
Adjuvant radiotherapy should be considered after complete surgical resection of WHO grade 2 atypical meningioma, the ROAM/EORTC-1308 phase 3 randomised trial concludes. The international, multicentre, open-label trial compared radiotherapy with observation and found radiotherapy reduces meningioma recurrence, trading that benefit against potential delayed adverse effects. The authors recommend decisions through individual discussion with each patient.
In the head-to-head REIMAGINE 5 trial, Novo Nordisk's CagriSema produced mean weight loss of 12.4% in patients with type 2 diabetes, versus 9.1% for Eli Lilly's tirzepatide. Both studies met their primary endpoints, safety was broadly consistent with prior trials, and no new safety signals were identified. The result positions CagriSema ahead of tirzepatide on weight loss, though it does not settle the broader competition between the two companies.
Novo Nordisk announced that CagriSema (cagrilintide and semaglutide) beat tirzepatide head-to-head on the primary endpoint of the phase-three REIMAGINE 5 trial. In parallel, the REDEFINE 9 trial showed CagriSema outperformed placebo on weight loss, also meeting its primary endpoint. The results position CagriSema as a challenger to tirzepatide in the obesity drug market.
Six of ten virologically suppressed chronic hepatitis B patients with HBsAg levels ≤200 IU/mL achieved HBsAg loss on a response-guided sequential strategy of the anti-PD-1 antibody sintilimab plus PEG-IFNα add-on, with all six maintaining HBsAg negativity 24 weeks after stopping treatment. HBsAg loss correlated with increased HBV-specific IL-2 and IFN-γ T-cell responses, and week-3 IL-10 levels associated with early ALT elevation and subsequent HBsAg decline. Adverse events were mostly grade 1-2.
A phase 2b/3 trial of Merck's FZD4/LRP5 bispecific antibody in diabetic macular edema met success, per the company. Merck built its ophthalmology pipeline around two assets, Remigromig and MK-8748, obtained through its $3 billion acquisition of EyeBio in May 2024. In July, MK-8748, a first-in-class VEGF/Tie2 bispecific also originally developed by EyeBio, entered two phase 3 DME trials head-to-head against aflibercept.
Faecal microbiota transplantation provided no clinical benefit over placebo in patients with irritable bowel syndrome in REFIT2, a randomised, double-blind, placebo-controlled phase 3 trial. The results suggest that modulating the microbiota alone may be insufficient to improve IBS symptoms. The finding shifts attention away from microbiota-only strategies for this condition.
Merck's remigromig, a trispecific Wnt-pathway agonist for diabetic macular edema, hit the primary endpoint in the phase 2b/3 Brunello trial: both doses were noninferior to ranibizumab at Week 52 on change in best-corrected visual acuity and were well tolerated. Rates of proliferative diabetic retinopathy, vitreous hemorrhage and discontinuations due to adverse events were higher on remigromig, and Merck is running further analyses. The candidate came with Merck's $3 billion acquisition of EyeBio.
Adding the CD47 inhibitor evorpacept to trastuzumab, ramucirumab and paclitaxel (TRP) produced a higher objective response rate than TRP alone in patients with HER2-positive advanced gastric cancer that had progressed on anti-HER2 treatment. The finding comes from the phase 2 part of the randomized ASPEN-06 trial. Response was associated with CD47 and HER2 expression.
A single dose of miv-cel (mivocabtagene autoleucel) produced durable benefit in stiff person syndrome, with 26 patients in the Kysa-8 registrational trial showing a median 49% improvement on the timed 25-foot walk test at 12 months versus baseline, up from 46% at week 16. There were zero cases of high-grade cytokine release syndrome, ICANS or IEC-HS, and 92% of patients remained free of chronic immunotherapies. Kyverna will add the one-year data to its FDA rolling submission, on track for completion in the fourth quarter.
Why it matters: One-year data support what could be the first approved CAR-T therapy for an autoimmune disease, with sustained efficacy and no severe toxicity.
Immunovant has stopped developing IMVT-1402 in cutaneous lupus erythematosus after the anti-FcRn antibody missed its primary endpoints in a phase 2 trial. In 57 adults with CLE, scores on a CLE area and severity scale at Week 12 were statistically no better than placebo, despite numerical trends favoring the drug and responses among patients with deeper IgG reductions. The drug showed favorable safety and remains in development for other indications including Graves' disease and myasthenia gravis.
Sefaxersen, an antisense oligonucleotide targeting complement factor B, met the primary endpoint in a prespecified interim analysis of the phase III MAgINATION study in IgA nephropathy. At week 37, the drug produced a statistically significant and clinically meaningful reduction in proteinuria versus placebo. It is the first RNA-targeted therapy for IgA nephropathy and the only CFB antisense therapy in development.
Anito-cel, a d-domain CAR T cell targeting BCMA, showed a favorable safety profile and preliminary efficacy in a phase 1 clinical trial for refractory or relapsed multiple myeloma. The study assessed the safety, tolerability, and antitumor activity of anito-cel at escalating dose levels. The findings support further clinical development of this therapy in patients with relapsed/refractory multiple myeloma.
Sefaxersen, a monthly subcutaneous antisense oligonucleotide inhibiting complement factor B, met the primary endpoint of a phase 3 trial in primary IgA nephropathy, significantly reducing proteinuria versus placebo at the Week 37 interim analysis. Safety and tolerability were consistent with earlier trials, and Roche plans regulatory talks, aiming for accelerated approval in a market where Novartis' oral factor B inhibitor Fabhalta is already fully authorized.
Celldex announced positive results for its monoclonal antibody in two phase 3 trials in patients with treatment-refractory chronic spontaneous urticaria. The drug's development had previously hit setbacks, and the double phase 3 success marks its return on track.
