Summit Therapeutics has announced significant progress in the clinical development of ivonescimab (SMT112), a bispecific antibody targeting both PD-1 and VEGF, for the treatment of non-small cell lung cancer (NSCLC). The company reported positive results from the Phase III HARMONi-2 trial and provided updates on ongoing and planned clinical trials evaluating ivonescimab in various NSCLC settings.
HARMONi-2 Trial Results
The Phase III HARMONi-2 trial, conducted by Akeso Inc. in China, evaluated ivonescimab monotherapy versus pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. The trial met its primary endpoint, demonstrating a 49% reduction in the risk of disease progression or death in patients receiving ivonescimab (HR: 0.51, 95% CI: 0.38 - 0.69; p<0.0001). The median progression-free survival (PFS) was 11.1 months for ivonescimab compared to 5.8 months for pembrolizumab. Clinically meaningful benefits were observed across pre-specified subgroups, including those with low and high PD-L1 expression and squamous and non-squamous histologies. The overall response rate (ORR) and disease control rate (DCR) were also higher in the ivonescimab arm. The safety profile of ivonescimab was reported as acceptable and manageable.
Ongoing and Planned Phase III Trials
Summit Therapeutics is currently conducting two Phase III trials and planning a third to further evaluate ivonescimab in NSCLC:
- HARMONi: This trial is evaluating ivonescimab combined with chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI). Enrollment is complete, and topline data is expected in mid-2025. The FDA has granted Fast Track Designation for ivonescimab in this setting.
- HARMONi-3: This trial is evaluating ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients without actionable genomic alterations. The protocol is being amended to include patients with both squamous and non-squamous histologies, with progression-free survival (PFS) and overall survival (OS) as co-primary endpoints. The total sample size will be increased to an estimated 1,080 patients.
- HARMONi-7: This planned trial will evaluate ivonescimab monotherapy versus pembrolizumab monotherapy in first-line metastatic NSCLC patients whose tumors have high PD-L1 expression. The trial is expected to initiate in early 2025 and will enroll an estimated 780 patients, with PFS and OS as co-primary endpoints.
Expansion into Other Solid Tumors
Based on encouraging Phase II data, Summit intends to explore further clinical development of ivonescimab in solid tumor settings outside of metastatic NSCLC, including advanced triple-negative breast cancer (TNBC), recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), and metastatic microsatellite-stable (MSS) colorectal cancer (CRC).
Financial Update
Summit Therapeutics reported a strengthened financial position with $487 million in cash, cash equivalents, and short-term investments as of September 30, 2024, including $235 million raised in a recent private financing. This is expected to support the expansion of ivonescimab trials planned for 2025.
