Ivonescimab Plus Chemotherapy Shows Improved Progression-Free Survival in Lung Cancer Study.

Summit Therapeutics reports positive results from the HARMONi trial of ivonescimab in combination with chemotherapy for EGFR-mutant non-small cell lung cancer. The trial demonstrates a 48% reduction in disease progression or death compared to chemotherapy alone, with a positive overall survival trend. Favorable trends were observed in sub-populations from North America and China. The company plans to determine the timing of a US BLA filing.

Summit Therapeutics Inc. (SMMT) announced positive topline results from the Phase III clinical trial, HARMONi, evaluating ivonescimab plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and a positive trend in overall survival (OS) [1].

The HARMONi study, a multiregional, double-blinded, placebo-controlled trial sponsored by Summit, evaluated ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with locally advanced or metastatic non-squamous NSCLC who had progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI). The study included approximately 38% of patients from western countries, consistent with other recent multiregional Phase III studies in patients with EGFR-mutated NSCLC [2].

Key findings from the HARMONi trial include:

- Ivonescimab in combination with chemotherapy reduced the risk of disease progression or death by 48% compared to chemotherapy alone.
- A hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p0.00001) was observed for PFS, indicating a statistically significant and clinically meaningful improvement.
- A positive trend in OS was noted with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057).
- Favorable trends in sub-populations from North America and China were observed for both primary endpoints.

The results of the primary analysis in the multiregional study were consistent with those of the single-region HARMONi-A study. No new safety signals were noted, and the safety profile of ivonescimab plus chemotherapy was considered acceptable and manageable in the context of the observed clinical benefit [2].

Based on the results of the HARMONi clinical trial, Summit intends to file a Biologics License Application (BLA) to seek approval for ivonescimab plus chemotherapy in this setting. The company will consider the timing of the BLA filing based on discussions with the United States Food & Drug Administration (FDA), which noted that a statistically significant overall survival benefit is necessary to support marketing authorization [1].

The positive Phase III HARMONi study results, along with the approval of ivonescimab in China, further substantiate the potential of ivonescimab to improve upon existing standards of care for solid tumors, including in settings where existing immune checkpoint inhibitors are indicated. The company expressed gratitude to the patients, physicians, nurses, and caregivers who participated in and supported the clinical study.

References:
[1] https://www.nasdaq.com/articles/summit-phase-iii-trial-ivonescimab-plus-chemotherapy-shows-positive-results-egfr-mutant
[2] https://www.morningstar.com/news/business-wire/20250530679531/ivonescimab-plus-chemotherapy-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-after-egfr-tki-therapy-in-global-study