Summit Therapeutics reports FDA refusal for lung cancer treatment
The agency found the progression-free survival benefit insufficient without statistically significant overall survival gains.
Adrian Kessler
Potential U.S. sales have been delayed after Summit Therapeutics Inc. NASDAQSMMT reported on Sunday that the FDA declined approval of ivonescimab plus chemotherapy for previously treated lung cancer. Its 438-patient HARMONi trial met the progression-free survival endpoint but missed the primary overall survival (OS) endpoint.
The complete response letter concerns patients with locally advanced or metastatic non-small cell lung cancer previously treated with an epidermal growth factor receptor inhibitor. According to Summit's account, the FDA concluded that the progression-free survival benefit could not establish a positive benefit-risk profile without a statistically significant overall survival improvement.
Summit is a Miami-based oncology drug developer with a multinational late-stage clinical program focused on ivonescimab, an experimental antibody combining immune-checkpoint and blood-vessel-growth blockade.
Summit shares NASDAQSMMT closed at US$14.15 on Nasdaq as of 4:00 p.m. EST on Nov. 13. That price precedes Sunday's disclosure and cannot measure investors' response to the refusal.
The Primary Survival Analysis Fell Short
HARMONi, identified as NCT06396065 in Summit's announcement, randomly assigned patients to ivonescimab or placebo, each combined with platinum-containing chemotherapy. The double-blind Phase 3 trial enrolled patients with EGFR-mutated, non-squamous cancer previously treated with a third-generation targeted inhibitor.
Summit's Sept. 15 trial update reported 219 patients in each arm. In the primary analysis, median overall survival was 16.8 months with ivonescimab plus chemotherapy against 14.0 months with placebo plus chemotherapy.
The survival hazard ratio was 0.79, with p=0.057. The 95 per cent confidence interval ranged from 0.62 to 1.01, encompassing no difference between the groups.
A post-hoc analysis using a June 2026 data cut produced a survival hazard ratio of 0.76 and a nominal p value of 0.0151. Those later findings did not change the FDA conclusion described in Sunday's release.
"The FDA indicated that the progression-free survival (PFS) benefit in the absence of a statistically significant OS benefit does not support a positive benefit-risk profile in support of approval," Summit said in its release.
Summit reported no new safety signals, but treatment-related adverse events caused four deaths in the ivonescimab arm and five in the control arm. The company had already disclosed the FDA's requirement for a statistically significant survival benefit before the decision.
Approved Treatments And Further Trials Remain In View
Johnson & Johnson NYSEJNJ announced FDA approval of Rybrevant plus chemotherapy on Sept. 19, 2024 for advanced lung cancer with specified EGFR mutations after prior targeted treatment. Its MARIPOSA-2 trial reported median progression-free survival of 6.3 months against 4.2 months with chemotherapy alone. Those results come from a separate study and do not establish how Rybrevant and ivonescimab compare directly.
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The wider oncology market includes Merck & Co., Inc. NYSEMRK, which reported third-quarter Keytruda and Keytruda Qlex sales of US$8.6 billion on Oct. 29. That combined figure covers multiple cancer indications rather than the lung cancer setting in Summit's application. Merck shares NYSEMRK stood at US$147.76 as of 4:02 p.m. EST on Nov. 13.
Summit's Nov. 4 financial update reported US$629.8 million in cash and investments at Sept. 30. The company said it subsequently received a further US$2 billion through an equity investment.
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The next dated clinical milestone is the fourth quarter of 2026, when Summit expects enough progression events in HARMONi-3's squamous lung cancer cohort for its primary analysis. An early survival analysis is planned alongside it, testing treatment in previously untreated metastatic disease.
