FDA Advances Ivonescimab for EGFR-TKI-Resistant Lung Cancer as New Treatment Option

Summit Therapeutics has achieved a significant regulatory milestone with the FDA’s acceptance of its biologics license application for ivonescimab, a novel therapy designed to address resistance to third-generation EGFR-TKI drugs in advanced lung cancer patients. The agency has designated November 14, 2026, as the target review completion date, marking a crucial step toward bringing this post-TKI treatment option to patients with EGFR-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

The regulatory pathway reflects the FDA’s commitment to comprehensive evaluation, with plans for mid-cycle and late-cycle discussions to ensure thorough assessment of the application prior to the final action date. If development proceeds smoothly without major concerns, preliminary labeling discussions could occur before the official review deadline.

How Ivonescimab Addresses Post-TKI Drug Resistance

Ivonescimab represents a first-in-class bispecific antibody that simultaneously targets PD-1 and VEGF pathways, offering a novel approach for patients whose tumors have developed resistance to first and second-line EGFR-TKI drugs. This dual-targeting strategy was developed through Summit’s collaboration with Akeso, a China-based biopharmaceutical company, with the licensing agreement finalized in January 2023.

The underlying mechanism behind ivonescimab’s design reflects growing understanding of how tumors evade EGFR-TKI therapy. By engaging both immune checkpoint (PD-1) and angiogenesis pathways (VEGF), the drug aims to overcome multiple resistance mechanisms simultaneously. This multi-pronged approach distinguishes it from conventional sequential therapies, which address resistance mechanisms one at a time.

The clinical evidence supporting this approach comes from the phase III HARMONi study, which evaluated ivonescimab plus platinum-doublet chemotherapy against placebo plus chemotherapy in patients with EGFR-mutated NSCLC who had progressed on standard EGFR-TKI therapy. While the study achieved its primary endpoint of improved progression-free survival, showing that patients receiving ivonescimab maintained disease control longer than the control group, the overall survival endpoint—previously identified as critical by regulatory authorities—demonstrated favorable trends without reaching statistical significance. This partial efficacy profile still provided sufficient clinical evidence for FDA advancement.

Expanding Development Beyond NSCLC

Summit’s clinical development strategy extends well beyond the current NSCLC indication. The company is actively pursuing three additional late-stage trials: HARMONi-3 and HARMONi-7, which examine ivonescimab in different NSCLC patient populations and treatment sequences.

More notably, the company initiated enrollment in the HARMONi-GI3 trial in late 2025, marking ivonescimab’s first venture into solid tumors beyond lung cancer. This phase III study evaluates the drug combined with chemotherapy against the established standard bevacizumab-chemotherapy combination in patients with first-line unresectable metastatic colorectal cancer. The trial’s primary objective focuses on progression-free survival, employing the same efficacy metric that demonstrated ivonescimab’s benefit in lung cancer studies.

The FDA previously granted Fast Track designation to ivonescimab for the HARMONi NSCLC program, acknowledging the unmet medical need in post-TKI therapy. Summit intends to provide comprehensive updates on additional planned development activities and timeline estimates during its first quarter 2026 investor communications.

Market Context and Stock Performance

Over the past twelve months, Summit shares have declined 28.4%, outperforming the overall industry decline of 1.3%—a performance gap that may reflect market concerns about advancing the drug through late-stage development, regulatory timelines, or commercial adoption challenges for post-EGFR-TKI therapies.

Within the broader biotech sector, peer-reviewed investment analysts maintain diverse assessments. Companies such as Assertio Holdings, Alkermes, and Soleno Therapeutics currently hold stronger analyst ratings, reflecting varied confidence levels regarding pipeline advancement and commercial prospects across the sector.

The regulatory acceptance of ivonescimab’s application represents an important validation point for Summit’s approach to addressing EGFR-TKI-resistant disease, particularly for the substantial patient population requiring effective post-TKI treatment options.