On January 29, 2026, Summit Therapeutics announced that the U.S. Food and Drug Administration has accepted for filing a Biologics License Application (BLA) seeking approval of ivonescimab in combination with platinum-based chemotherapy for patients with epidermal growth factor receptor–mutated (EGFRm) locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) following progression on prior tyrosine kinase inhibitor (TKI) therapy.
The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026, marking an important regulatory step for ivonescimab in a setting where therapeutic options remain limited.
The Agency indicated that it intends to conduct a full review of the application in accordance with draft guidance and Good Review Management Principles and Practices, including planned mid-cycle and late-cycle meetings, barring identification of major deficiencies during the review process.
Read About Non-Small Cell Lung Cancer on OncoDaily
Unmet Need in EGFR-Mutated NSCLC After TKI Progression
EGFR-mutated NSCLC represents a distinct molecular subset of lung cancer with established sensitivity to EGFR TKIs in the frontline setting. However, disease progression after third-generation EGFR TKIs, such as osimertinib, remains inevitable for most patients. Following TKI failure, treatment options are largely limited to platinum-based chemotherapy, with modest efficacy and no universally accepted targeted or immunotherapy standard.
According to Summit Therapeutics, more than 14,000 patients in the United States may be eligible each year for treatment in this post-TKI setting, highlighting the substantial unmet clinical need addressed by the ivonescimab development program.
Clinical Basis for the BLA: The HARMONi Phase III Trial
The BLA submission is supported by results from HARMONi, a global, randomized, phase III study evaluating ivonescimab in combination with platinum-doublet chemotherapy versus placebo plus chemotherapy. The trial enrolled patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed after treatment with a third-generation EGFR TKI.
Detailed efficacy and safety results from HARMONi were disclosed in September 2025 and demonstrated clinically meaningful benefit, forming the basis for the regulatory filing. The FDA acceptance confirms that the application is sufficiently complete to permit a substantive review, though it does not imply approval.
Ivonescimab has also received Fast Track designation from the FDA for this clinical setting, reflecting the seriousness of the disease and the potential for the therapy to address unmet medical needs.
Read About HARMONi Trial on OncoDaily
Ivonescimab: Mechanism and Molecular Design
Ivonescimab is a novel, potential first-in-class bispecific antibody designed to simultaneously target programmed death-1 (PD-1) and vascular endothelial growth factor (VEGF) within a single molecule. Outside Summit’s licensed territories, the drug is known as AK112 and was engineered by Akeso.
The antibody’s tetravalent structure, featuring four binding sites, enables cooperative and high-avidity binding to both PD-1 and VEGF. Preclinical and translational studies suggest that ivonescimab has higher functional affinity for PD-1 in the presence of VEGF, a design feature intended to preferentially localize activity within the tumor microenvironment, where both targets are often highly expressed.
This dual-pathway inhibition aims to integrate immune checkpoint blockade with anti-angiogenic effects, potentially enhancing antitumor immunity while simultaneously disrupting tumor vasculature. Ivonescimab’s pharmacokinetic profile includes an initial half-life of approximately six to seven days after the first dose, increasing to around ten days at steady state, supporting its dosing strategy in combination regimens.
Broader Phase III Development Program
Ivonescimab is currently one of the most extensively studied bispecific antibodies in late-stage oncology development. To date, more than 4,000 patients have received ivonescimab in clinical trials globally, and over 60,000 patients have been treated when including commercial use in China.
Beyond HARMONi, Summit Therapeutics is conducting multiple global phase III studies, including HARMONi-3, which compares ivonescimab plus chemotherapy with pembrolizumab plus chemotherapy in first-line metastatic NSCLC regardless of PD-L1 expression, and HARMONi-7, evaluating ivonescimab monotherapy versus pembrolizumab in patients with high PD-L1–expressing tumors.
In addition, the development program has expanded into gastrointestinal malignancies, with HARMONi-GI3 evaluating ivonescimab plus chemotherapy versus bevacizumab plus chemotherapy in first-line unresectable metastatic colorectal cancer.
Single-region phase III studies conducted by Akeso in China, including HARMONi-A, HARMONi-2, and HARMONi-6, have also reported positive outcomes, including statistically significant overall survival benefit in EGFR-mutated NSCLC with manageable safety profiles.
Regulatory Status and Global Context
Ivonescimab remains investigational in the United States and Europe and is not yet approved in Summit’s licensed territories. The drug received marketing authorization in China in May 2024, providing real-world experience that complements ongoing global clinical development.
The FDA’s acceptance of the BLA represents a key regulatory milestone and initiates the formal review process. Final approval will depend on the Agency’s assessment of the totality of evidence regarding efficacy, safety, and benefit–risk balance.
Outlook Toward the PDUFA Date
With a PDUFA goal date of November 14, 2026, ivonescimab now enters a critical phase of regulatory evaluation. If approved, ivonescimab plus chemotherapy could represent a novel treatment option for patients with EGFR-mutated NSCLC who progress after EGFR TKI therapy, a population with limited effective alternatives.
As the review proceeds, the oncology community will closely follow further disclosures related to labeling discussions, safety considerations, and potential positioning relative to existing post-TKI treatment strategies.
Written by Armen Gevorgyan, MD