Summit Therapeutics (SMMT) Status update summary

HARMONi-6 Phase III Trial Results

• Ivonescimab plus chemotherapy demonstrated a statistically significant overall survival benefit over tislelizumab plus chemotherapy in advanced squamous non-small cell lung cancer, with a hazard ratio of 0.66 and median OS of 27.89 vs. 23.69 months; 24-month OS rates were 64.7% vs. 48.6%.

• The OS benefit was consistent across all PD-L1 expression subgroups, with hazard ratios of 0.64–0.68, and across key clinical subgroups including age, sex, ECOG PS, disease stage, and metastatic burden.

• The trial enrolled 532 patients, predominantly male, with high-risk features for bleeding; baseline characteristics were well balanced between arms.

• This is the first randomized phase III trial to show OS benefit over another PD-1 therapy plus chemotherapy in this setting, suggesting ivonescimab could become a new standard of care.

• Results were presented at ASCO 2026 and published in The Lancet.

Safety Profile

• Ivonescimab plus chemotherapy had a manageable safety profile, with grade ≥3 TRAEs in 69.2% vs. 58.9% for tislelizumab; serious adverse events occurred in 41.4% vs. 34.3%.

• Most VEGF-related adverse events were mild (grade 1-2), but grade 3 or higher hemorrhage events were 2.6% for ivonescimab vs. 0.8% for tislelizumab.

• Discontinuation due to adverse events was 5.3% for ivonescimab and 4.5% for tislelizumab.

• No new safety signals were observed; adverse events were manageable and comparable between arms.

• Serious TRAEs and rates of discontinuation or death were similar between arms.

Study Design and Patient Characteristics

• Phase III, multicenter, randomized, double-blind trial compared ivonescimab plus chemotherapy to tislelizumab plus chemotherapy in untreated advanced squamous NSCLC (N=532).

• Key eligibility: stage IIIB-IV, ECOG PS 0-1, no prior systemic therapy, no EGFR/ALK alterations.

• Baseline characteristics were well balanced between arms, including age, sex, disease stage, and PD-L1 expression.

• Subgroup imbalances in HARMONi-6 (e.g., age, lesion size, brain metastases) were addressed by covariate analysis, showing no detriment in older patients after adjustment.

• Subgroup analyses confirmed broad benefit not driven by any specific subset.