Summit Therapeutics announced positive results from the Phase III HARMONi-2 trial, revealing that ivonescimab monotherapy significantly improved progression-free survival (PFS) compared to pembrolizumab in patients with PD-L1 positive advanced non-small cell lung cancer (NSCLC). The study, conducted in China by Akeso, Inc., demonstrated a 49% reduction in the risk of disease progression or death, marking a potential shift in first-line treatment options.
HARMONi-2 Trial Results
The HARMONi-2 trial (n=398) evaluated ivonescimab monotherapy against pembrolizumab monotherapy in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression (PD-L1 TPS >1%). The primary endpoint, PFS, showed a statistically significant improvement with ivonescimab, achieving a hazard ratio (HR) of 0.51 (95% CI: 0.38, 0.69; p<0.0001). Median PFS was 11.14 months for ivonescimab compared to 5.82 months for pembrolizumab.
Professor Caicun Zhou, MD, PhD, who presented the data at the World Conference on Lung Cancer (WCLC) 2024, highlighted the clinically meaningful benefit observed across various clinical subgroups, including those with low and high PD-L1 expression, as well as squamous and non-squamous histologies.
| Metric | Ivonescimab (n=198) | Pembrolizumab (n=200) |
| --------------------------- | --------------------- | ----------------------- |
| Median PFS | 11.14 months | 5.82 months |
| PFS Stratified HR | 0.51 (p<0.0001) | - |
| Overall Response Rate (ORR) | 50.0% | 38.5% |
| Disease Control Rate (DCR) | 89.9% | 70.5% |
Safety Profile
Ivonescimab demonstrated a manageable safety profile consistent with previous studies. Treatment-related adverse events (TRAEs) leading to discontinuation were less frequent with ivonescimab (1.5%) compared to pembrolizumab (3.0%). However, Grade 3 or higher adverse events possibly related to VEGF were more frequent in the ivonescimab arm (10.2%) versus the pembrolizumab arm (1.0%).
HARMONi-7 and Future Plans
Based on these results, Summit Therapeutics plans to initiate HARMONi-7, a multi-regional Phase III clinical trial, in early 2025. This trial will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%).
Dr. Maky Zanganeh, CEO and President of Summit, stated that ivonescimab has the potential to be the next generation in PD-1 directed immunotherapy, potentially making a significant difference in the lives of patients with lung cancer and other tumors.
Perioperative NSCLC Data
Additional Phase II data presented at WCLC 2024 highlighted the potential of ivonescimab in the perioperative setting. In patients with resectable NSCLC, neoadjuvant treatment with ivonescimab plus chemotherapy resulted in a major pathological response (MPR) in 71.8% of patients and a pathological complete response (pCR) in 43.6% of patients.
Upcoming Presentations at ESMO 2024
Further Phase II data featuring ivonescimab in triple-negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), and colorectal cancer (CRC) will be presented at the European Society of Medical Oncology (ESMO) Congress 2024.
