Summit Therapeutics Inc. announced that the first United States-based patient has been enrolled in the Phase III HARMONi study. HARMONi is a Phase III multiregional, randomized, double-blinded study. The study will evaluate the efficacy and safety of ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR) -mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) such as osimertinib.

Specifically, the study will compare ivonescimab combined with pemetrexed and carboplatin chemotherapies against a placebo plus pemetrexed and carboplatin. The study, designed with registration intent, has two primary endpoints: overall survival (OS) and progression-free survival (PFS). HARMONi, also referred to as AK112-301, will enroll patients from the United States, Canada, Europe, and China in conjunction with the company's high-achieving partner, Akeso Inc. (Akeso).

Akeso is responsible for enrollment in China, which has previously commenced; Summit is responsible for enrollment in the United States, Canada, and Europe. Over 400 patients are planned to be enrolled in the study. Ivonescimab, known as SMT112 in the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule.

There is higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal, healthy tissue in the body. Ivonescimab's tetravalent structure enables higher avidity (accumulated strength of multiple binding interactions) with over 10 fold increased binding affinity to PD-1 in the presence of VEGF in vitro in tumor cells.1 This tetravalent structure, the design of the molecule, and bringing these two targets into a single bispecific antibody have the potential to steer ivonescimab to the tumor tissue versus healthy tissue, which are intended to improve side effects and safety concerns associated with these targets and have the potential to focus the antitumor activity of both targets. look forward to continuing to share additional details regarding ivonescimab at upcoming medical conferences.