First-line treatment shows significant improvement in progression-free survival over pembrolizumab, marking a potential shift in NSCLC care
Summit Therapeutics (SMMT) has announced promising results from its Phase III HARMONi-2 trial, which evaluated ivonescimab, a novel bispecific antibody, in comparison to pembrolizumab as a first-line treatment for advanced non-small cell lung cancer (NSCLC). The results, presented at the 2024 World Conference on Lung Cancer (WCLC) in San Diego, highlight a significant improvement in progression-free survival (PFS) for patients receiving ivonescimab, positioning the drug as a potential game-changer in lung cancer immunotherapy.
Ivonescimab Demonstrates Superior Efficacy Over Pembrolizumab
The HARMONi-2 trial compared ivonescimab monotherapy with pembrolizumab in patients with locally advanced or metastatic NSCLC who exhibited PD-L1 positive expression (PD-L1 TPS >1%). Ivonescimab demonstrated a marked improvement in the primary endpoint of progression-free survival (PFS). The trial’s Independent Radiologic Review Committee (IRRC) reported a median PFS of 11.14 months for patients receiving ivonescimab, compared to 5.82 months for those treated with pembrolizumab. This resulted in a hazard ratio of 0.51 (95% CI: 0.38, 0.69; p<0.0001), representing a statistically significant improvement.
The efficacy of ivonescimab was observed across various clinical subgroups, including both low (PD-L1 TPS 1-49%) and high (PD-L1 TPS ≥ 50%) PD-L1 expressing tumors, as well as squamous and non-squamous histologies. Additionally, the overall response rate (ORR) and disease control rate (DCR) were higher for ivonescimab compared to pembrolizumab, further underscoring its potential as a more effective treatment option for a broader range of NSCLC patients.
“This is a historic moment for ivonescimab, Summit, our partners at Akeso, and most importantly, for patients living with cancer,” said Robert W. Duggan, Chairman and Chief Executive Officer of Summit. “The data from HARMONi-2 suggests that ivonescimab could be the next generation of PD-1-directed immunotherapy, offering a significant clinical benefit over pembrolizumab.”
A Manageable Safety Profile
Ivonescimab demonstrated a manageable safety profile consistent with earlier studies. While there were adverse events related to treatment, the overall safety data suggest that ivonescimab is well-tolerated. In the trial, 1.5% of patients discontinued ivonescimab due to treatment-related adverse events (TRAEs), compared to 3.0% of patients in the pembrolizumab arm. The most frequent TRAEs in the ivonescimab arm were hypertension and proteinuria, with 5.1% and 3.0% of patients experiencing Grade 3 or higher instances, respectively. Immune-related adverse events occurred in 7.1% of patients treated with ivonescimab, compared to 8.0% in the pembrolizumab group.
The results indicate that, while ivonescimab is associated with some VEGF-related adverse events, such as Grade 3 hemorrhage, the overall safety profile remains acceptable for a drug showing such robust efficacy in lung cancer treatment.
Looking Ahead: HARMONi-7 and Expanded Clinical Development
Following the success of HARMONi-2, Summit plans to initiate HARMONi-7, a multi-regional Phase III clinical trial in early 2025. HARMONi-7 will focus on comparing ivonescimab with pembrolizumab in patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%).
“We are excited to advance ivonescimab into further clinical trials and expand its development across various tumor types,” said Dr. Maky Zanganeh, Chief Executive Officer and President of Summit. “We look forward to sharing additional details about our clinical plans in early 2025.”
Additional Data from Perioperative NSCLC Studies
In addition to the HARMONi-2 results, a second oral presentation at WCLC 2024 focused on ivonescimab’s role in perioperative settings. The Phase II study, AK112-205, evaluated ivonescimab alone or in combination with chemotherapy for patients with resectable NSCLC. In the neo-adjuvant setting, ivonescimab plus chemotherapy showed promising results, with a major pathological response (MPR) rate of 71.8% and a pathological complete response (pCR) rate of 43.6%.
These findings suggest that ivonescimab could play a pivotal role in both pre- and post-surgery settings for NSCLC patients, potentially improving long-term outcomes and survival rates.
A Broader Impact on Cancer Treatment
Beyond NSCLC, Summit and its partner Akeso are preparing to present additional Phase II data at the European Society of Medical Oncology (ESMO) Congress 2024. The upcoming presentations will highlight ivonescimab’s potential in treating other cancers, including triple-negative advanced breast cancer, head and neck squamous cell carcinoma, and colorectal cancer.
With ivonescimab showing consistent efficacy and safety across multiple clinical trials, Summit Therapeutics and Akeso are positioning the drug to potentially reshape the landscape of cancer treatment. If future trials confirm its benefits, ivonescimab could offer a new, more effective treatment option for cancer patients worldwide.
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