Summit Therapeutics' Ivonescimab Shows Promise in Global Phase III Trial Despite Missing Survival Endpoint.

Summit Therapeutics' investigational bispecific antibody, ivonescimab, has shown encouraging results in the global Phase III HARMONi trial, targeting patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have progressed after third-generation tyrosine kinase inhibitor (TKI) therapy.

The trial met one of its co-primary endpoints, demonstrating a 48% reduction in the risk of disease progression or death compared to chemotherapy alone. This marks a significant milestone, indicating that the efficacy observed in Chinese trials can be replicated in a global patient population.

However, ivonescimab did not achieve statistical significance in overall survival (OS), the other co-primary endpoint. This outcome raises questions about its approvability in the U.S., where the FDA typically requires a statistically significant OS benefit for approval.

Despite this, analysts at Truist Securities remain optimistic, noting the consistency of ivonescimab's efficacy across Eastern and Western populations. They believe the data supports the potential for regulatory approval in both the U.S. and European Union. 

Summit Therapeutics, in collaboration with Chinese partner Akeso, has been at the forefront of developing PD-1/VEGF bispecific antibodies. Ivonescimab combines immunotherapy via PD-1 blockade with anti-angiogenesis effects by targeting VEGF, aiming to enhance anti-tumor activity. 

The HARMONi trial enrolled patients globally, with approximately 38% from Western countries. Participants received ivonescimab or placebo alongside platinum-doublet chemotherapy. While progression-free survival benefits were significant, the OS data, though favoring ivonescimab, did not reach statistical significance.

In response to the trial results, Summit's stock experienced a decline, reflecting investor concerns about the lack of a statistically significant OS benefit. Nonetheless, the company plans to file for FDA approval, considering the timing carefully in light of regulatory requirements. 

Beyond the HARMONi trial, Summit is conducting additional Phase III studies, including HARMONi-3, which compares ivonescimab plus chemotherapy to pembrolizumab plus chemotherapy in first-line metastatic squamous NSCLC patients. These trials aim to further evaluate ivonescimab's efficacy across different NSCLC subtypes.

The development of ivonescimab represents a significant advancement in NSCLC treatment, particularly for patients with limited options post-TKI therapy. While challenges remain, the promising progression-free survival data and cross-regional efficacy provide a strong foundation for potential regulatory approval and future clinical applications.

Source:https://www.biospace.com/drug-development/summits-bispecific-misses-survival-endpoint-in-global-phase-iii-trial-but-analysts-remain-optimistic

This is non-financial/medical advice and made using AI so could be wrong.