Phase 3 INTerpath-009 Trial of mRNA-4157 Plus Pembrolizumab for NSCLC Begins Recruitment

The pivotal phase 3 INTerpath-009 trial has begun global recruitment, with the first patients now beginning to enroll in Canada, according to an announcement from Merck and Moderna.

The randomized trial is evaluating the investigational individualized neoantigen therapy V940 (mRNA-4157) in combination with pembrolizumab as an adjuvant treatment for patients with resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after receiving neoadjuvant pembrolizumab plus platinum-based chemotherapy.

“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. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a statement. “We are pleased to expand the INTerpath clinical trial program with Moderna, evaluating V940 (mRNA-4157), a promising new modality, in combination with KEYTRUDA to pursue meaningful advances for lung cancer and bring more options to patients with earlier stages of disease, where we potentially can have the most impact.”

V940 is a novel investigational mRNA-based individualized neoantigen therapy consisting of “a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor,” officials explained in the announcement. “Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.”

The trial investigators will randomize adults 1:1 after surgical resection to receive V940 1 mg every three weeks for up to nine doses plus pembrolizumab 400 mg every six weeks for up to seven cycles, or placebo plus pembrolizumab. Disease-free survival is the primary endpoint of the study, with secondary endpoints including overall survival, distant metastasis-free survival, lung cancer-specific survival, safety, and quality of life.

Key eligibility criteria for the phase 3 INTerpath-009 trial includes a histologically/cytologically confirmed diagnosis of Stage II, IIIA, or IIIB (N2) NSCLC per the American Joint Committee on Cancer 8th Edition, an Eastern Cooperative Oncology Group performance status of 0 or 1, no pCR by local testing after neoadjuvant chemotherapy plus pembrolizumab, completed surgery with no disease by baseline imaging, and no EGFR mutation.

Merck and Moderna have also initiated phase 3 randomized clinical trials evaluating the combination as an adjuvant treatment in patients with resected high-risk melanoma (INTerpath-001) and NSCLC (INTerpath-002).

“We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC,” Kyle Holen, MD, Moderna’s senior vice president and head of development, Therapeutics and Oncology, said in a statement. “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.”

Source: Merck