Ivonescimab + Chemo Outperforms PD-1 Combo in 1L Squamous NSCLC in Akeso’s HARMONi-6 Study
Summit Therapeutics Inc. (NASDAQ: SMMT) has announced that Akeso, Inc. (HKEX: 9926.HK) has successfully met the primary endpoint of progression-free survival (PFS) in its Phase III clinical trial, HARMONi-6 (AK112-306). This study evaluates ivonescimab in combination with platinum-based chemotherapy compared to tislelizumab, a PD-1 inhibitor, combined with platinum chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC), regardless of PD-L1 expression. The trial, conducted exclusively in China, was sponsored by Akeso, with all data generated, managed, and analyzed by the company.
The trial’s prespecified interim analysis, performed by an Independent Data Monitoring Committee, showed that ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in PFS, based on blinded independent central radiology review (BICR), compared to the tislelizumab-chemotherapy combination. This benefit was observed in both PD-L1-positive and PD-L1-negative tumor patients. Akeso also noted that no new safety signals emerged in the study. The full data set from HARMONi-6 is expected to be presented at a major medical conference later in the year.
Before the success of HARMONi-6, there had been no Phase III studies that demonstrated a statistically significant improvement over PD-(L)1 inhibitor therapies combined with chemotherapy in head-to-head trials. This marks the second major breakthrough for ivonescimab, following the HARMONi-2 study, which showed a PFS benefit in a monotherapy setting for patients with PD-L1-positive squamous or non-squamous tumors. These results position ivonescimab-based regimens as the first investigational therapies to show superior efficacy compared to standard PD-(L)1 inhibitors combined with chemotherapy.
Dr. Maky Zanganeh, President and Co-CEO of Summit Therapeutics, commented on the achievement, stating, “Ivonescimab has the opportunity to make a significant, positive difference, potentially providing patients with the next generation of treatment options against solid tumors, starting with non-small cell lung cancer.”
Summit Therapeutics is currently enrolling patients in the HARMONi-3 study, a Phase III clinical trial designed to compare ivonescimab plus chemotherapy to pembrolizumab (an anti-PD-1 antibody) combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. This global study is being conducted with registrational intent for the U.S. and other regions where Summit holds license rights.
Summit’s Chairman and Co-CEO, Robert W. Duggan, expressed pride in the success of Akeso’s HARMONi-6 trial, adding, “Our aligned mission with Akeso seeks to bring ivonescimab to as many patients around the world as quickly as possible, and we are incredibly proud of Akeso’s accomplishment.”
About Ivonescimab
Ivonescimab (known as SMT112 in Summit’s territories, including North America, South America, Europe, the Middle East, Africa, and Japan) is a novel bispecific antibody under investigation as a first-in-class immunotherapy for NSCLC. Combining PD-1 inhibition with anti-angiogenesis through VEGF blockade, ivonescimab has shown cooperative binding to both targets, providing potentially higher efficacy in the tumor microenvironment (TME). This enhanced binding could lead to a more efficient and targeted treatment, distinguishing ivonescimab from conventional therapies that target only one of these pathways.
The tetravalent structure of ivonescimab, with four binding sites, allows higher avidity, or stronger interaction, to the TME compared to normal tissues. This unique design aims to improve efficacy and safety profiles, providing a more effective therapy with fewer side effects. The drug’s half-life of 6 to 7 days after the first dose further contributes to its potential as a next-generation therapeutic. Ivonescimab is currently being tested in multiple Phase III clinical trials, with over 2,300 patients having been treated globally.
Summit’s Ongoing Clinical Development
Summit has continued its development of ivonescimab in NSCLC with several ongoing Phase III trials. The HARMONi study focuses on evaluating ivonescimab combined with chemotherapy versus placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC. Top-line results from this study are expected to be announced in mid-2025. Meanwhile, the HARMONi-7 trial will evaluate ivonescimab monotherapy against pembrolizumab monotherapy in patients with high PD-L1 expression in first-line metastatic NSCLC.
Summit’s ongoing HARMONi-3 and HARMONi-7 studies aim to further establish ivonescimab as a key treatment in the global fight against NSCLC. In addition, Akeso has seen success in other Phase III trials in China, including HARMONi-A, HARMONi-2, and HARMONi-6, which evaluated various regimens for NSCLC patients.
Regulatory Status
Ivonescimab is not yet approved by any regulatory body in Summit’s territories, including the U.S. and Europe. However, the therapy received approval for marketing in China in May 2024. Ivonescimab has also received Fast Track designation from the U.S. FDA for its use in the HARMONi clinical trials.
Summit Therapeutics remains focused on advancing ivonescimab through ongoing clinical trials and looks forward to further expanding its reach to treat patients with non-small cell lung cancer and other solid tumors.
