HARMONi-2: Ivonescimab vs. Pembrolizumab to Feature in WCLC 2024 Symposium

Summit Therapeutics Inc. (NASDAQ: SMMT) has announced the primary analysis results of the Phase III HARMONi-2 trial, which will be presented at the International Association for the Study of Lung Cancer’s 2024 World Conference on Lung Cancer (WCLC 2024) in San Diego, California. The featured investigational bispecific antibody, ivonescimab, is poised to be a potential first-in-class treatment. The presentation is scheduled for September 8, 2024.

The HARMONi-2 trial compared ivonescimab monotherapy with pembrolizumab monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have tumors expressing PD-L1 (PD-L1 TPS >1%). This multi-center, double-blinded Phase III study was conducted in China and sponsored by Akeso, Inc., Summit's collaboration partner, and is notable for being the first Phase III trial to demonstrate statistically significant efficacy improvements over pembrolizumab in a head-to-head setting.

On May 30, 2024, Akeso reported that ivonescimab monotherapy significantly improved progression-free survival (PFS) compared to pembrolizumab. The PFS benefit was consistent across various clinical subgroups, including those with both low and high PD-L1 expression, different histologies, and other high-risk patient categories.

Dr. Caicun Zhou, a prominent figure in medical oncology and President-Elect of IASLC, will present the trial results. Another significant presentation at the conference will cover the Phase II trial, AK112-205, which explores the use of ivonescimab alone or in combination with chemotherapy for resectable NSCLC, addressing early-stage disease settings.

Ivonescimab, also referred to as SMT112 in Summit’s territories and AK112 in China and Australia, is a bispecific antibody combining immunotherapy via PD-1 blockade with anti-angiogenesis effects through VEGF inhibition. This dual-action molecule has shown higher binding affinity when both PD-1 and VEGF are present, potentially offering more targeted therapy to tumor tissues over normal tissues. The antibody’s tetravalent structure enables stronger binding in the tumor microenvironment, which could improve efficacy and safety profiles over existing treatments.

Ivonescimab's innovative design and cooperative binding features aim to enhance therapeutic effectiveness while minimizing adverse effects. Engineered by Akeso Inc., ivonescimab is currently undergoing various Phase III clinical trials worldwide, with over 1,800 patients treated so far.

Summit has initiated clinical development of ivonescimab in NSCLC within its licensed regions and started enrollment in two multi-regional Phase III trials, HARMONi and HARMONi-3, in 2023. The HARMONi trial will evaluate ivonescimab combined with chemotherapy against a placebo in patients with EGFR-mutated, advanced NSCLC who have progressed after a third-generation EGFR TKI treatment. The HARMONi-3 trial aims to compare ivonescimab combined with chemotherapy to pembrolizumab combined with chemotherapy in first-line metastatic squamous NSCLC patients.

Furthermore, two single-region Phase III trials conducted in China have shown positive results. The HARMONi-A trial evaluated ivonescimab with chemotherapy versus a placebo in advanced NSCLC patients with EGFR mutations. The HARMONi-2 trial, as mentioned, assessed ivonescimab monotherapy against pembrolizumab in advanced NSCLC patients with positive PD-L1 expression.

Currently, ivonescimab is an investigational treatment not approved by any regulatory authority in Summit’s licensed territories, including the United States and Europe. However, it received marketing authorization in China in May 2024.

Summit Therapeutics, headquartered in Miami, Florida, focuses on developing and commercializing oncology treatments that aim to improve patients' quality of life and address unmet medical needs. Founded in 2003, the company is listed on the NASDAQ Global Market under the symbol "SMMT".