A Phase 3 clinical trial, known as INTerpath-009, has been launched to investigate the efficacy of an individualized neoantigen therapy, V940 (mRNA-4157), in combination with Keytruda (pembrolizumab) for the adjuvant treatment of non-small cell lung cancer (NSCLC). This trial targets patients with resectable stage 2, 3A, or 3B NSCLC who have not achieved a pathological complete response following neoadjuvant treatment with Keytruda plus platinum-based chemotherapy. The study is being conducted globally, with initial patients enrolled in Canada.
The rationale behind this approach lies in the creation of individualized neoantigen therapies designed to stimulate antitumor immune responses. These therapies leverage T-cell responses based on the unique mutations present within a patient's tumor. Neoantigens, which are proteins that arise on cancer cells due to specific mutations in tumor DNA, can potentially trigger the body's immune system to target and attack these cancer cells.
Trial Design and Objectives
The INTerpath-009 trial aims to enroll 680 patients with resected stage 2, 3A, or 3B NSCLC who did not achieve a pathological complete response to prior treatment with Keytruda and platinum-based chemotherapy. Key eligibility criteria include an Eastern Cooperative Oncology Group performance status of 0 or 1 and the absence of EGFR mutations. Following surgical resection, participants will be randomized to receive either V940 plus Keytruda or placebo plus Keytruda.
The primary endpoint of the trial is disease-free survival, defined as the time from randomization to any recurrence, the occurrence of a new primary NSCLC, or death from any cause, whichever occurs first. Secondary endpoints include distant metastasis-free survival, overall survival, lung cancer-specific survival, disease-free survival after the next line of therapy, quality of life, and safety. The estimated primary completion date for the trial is May 16, 2033.
Expert Commentary
Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development at Merck Research Laboratories, emphasized the importance of this research, stating, "While the overall survival rates for patients with non-small cell lung cancer have significantly improved in recent years, lung cancer continues to be the leading cause of cancer death worldwide."
Dr. Kyle Holen, Senior Vice President and Head of Development, Therapeutics and Oncology at Moderna, added, "We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer, and together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy."
