Ivonescimab (SMT112) plus platinum-doublet chemotherapy maintained a consistent overall survival (OS) benefit vs placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) previously treated with a third-generation EGFR TKI, according to an updated analysis of the phase 3 HARMONi trial (NCT05184712).1
At the June 2026 data cutoff, the addition of ivonescimab to chemotherapy produced an OS HR of 0.76 in both the full intention-to-treat (ITT) population (n = 438) and the subgroup of Western patients (n = 165), by which point most Western patients had discontinued treatment or completed 2 years of therapy.
Full OS data and corresponding confidence intervals for this cutoff are intended to be presented at an upcoming medical meeting.
“The positive results from this latest overall survival analysis in the global HARMONi study continue to support the translation of the therapeutic profile of ivonescimab across the globe, including western patients from North America and Europe,” Maky Zanganeh, PhD, president and co-chief executive officer of Summit Therapeutics, stated in the news release. “We have made this updated analysis available to the FDA as we continue to progress our BLA filing for the potential approval of ivonescimab in the U.S.”
In January 2026, a biologics license application seeking the approval of ivonescimab in combination with chemotherapy in the second-line or later for patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC
In the primary OS analysis conducted in April 2025, ivonescimab plus chemotherapy generated a positive trend that did not reach statistical significance, with an HR of 0.79 (95% CI, 0.62-1.01; P = .057).1 The median OS was 16.8 months with ivonescimab plus chemotherapy vs 14.0 months with placebo plus chemotherapy. At that cutoff, the median follow-up for Western patients was 9.2 months—shorter than the median OS—whereas Asian patients had a median follow-up of 32.7 months, and the OS HR in the Western subgroup was 0.98.
A subsequent analysis in September 2025 extended Western patient follow-up to a median of 13.7 months and yielded an OS HR of 0.78 (95% CI, 0.62-0.98; nominal P = .0332), consistent with the primary analysis, with median OS unchanged in both arms. The OS HR in the Western subgroup improved to 0.84 at this cutoff.
In the June 2026 analysis, median follow-up for Western patients reached 23.2 months, and the Western subgroup HR converged with the ITT population at 0.76; the Asian cutoff remained locked at a median follow-up of 32.7 months.
According to Summit, the improving hazard ratios in the Western subgroup across the April 2025, September 2025, and June 2026 analyses reflect longer-term follow-up, bringing the magnitude of OS benefit in Western patients in line with that observed in patients enrolled in Asia.
HARMONi was a randomized, double-blind, multicenter, phase 3 trial evaluating ivonescimab or placebo in combination with pemetrexed and carboplatin in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC who experienced disease progression following treatment with an EGFR TKI, including third-generation agents such as osimertinib (Tagrisso).1,3
Patients were randomly assigned 1:1 to receive ivonescimab or placebo plus chemotherapy, with 219 patients in each arm of the ITT population.1
The trial featured dual primary end points of PFS and OS.2
HARMONi previously met its co-primary end point of PFS, demonstrating a statistically significant benefit with ivonescimab plus chemotherapy in the primary analysis.1
Ivonescimab is a novel, potential first-in-class investigational bispecific antibody that combines PD-1 blockade with anti-angiogenic VEGF inhibition in a single molecule, and is designed to display cooperative, higher-affinity binding to PD-1 in the presence of VEGF. The agent was engineered by Akeso and was first approved for marketing in China in May 2024.
