Moderna and Merck have announced median five-year follow-up data from the phase IIb KEYNOTE-942/mRNA-4157-P201 study, evaluating intismeran autogene (mRNA-4157 or V940), an investigational mRNA-based Individualised Neoantigen Therapy (INT), in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with high-risk melanoma (stage III/IV) following complete resection.

In this pre-planned analysis, adjuvant treatment with intismeran autogene, in combination with KEYTRUDA, continued to demonstrate sustained and clinically meaningful improvement in the study’s primary endpoint, Recurrence-Free Survival (RFS), reducing the risk of recurrence or death by 49 percent (HR=0.510; [95% CI, 0.294–0.887]; one-sided nominal p=0.0075) compared to KEYTRUDA alone. The companies plan to present further data from follow up analyses of primary and secondary endpoints at an upcoming medical meeting. 

“Now with five years of follow-up data, today’s results highlight the potential of a prolonged benefit of the intismeran autogene and KEYTRUDA combination in patients with resected high-risk melanoma. We continue to invest in our platform in oncology because of encouraging outcomes like these, which illustrate mRNA’s potential in cancer care. We look forward to several additional milestones to come, including the results of our phase III study in adjuvant melanoma in collaboration with Merck, and continued progress across the eight phase II and phase III studies in multiple tumour types and patient populations,” said Kyle Holen, MD, Senior Vice President and Head of Development—Oncology and Therapeutics, Moderna.  

This analysis from the phase 2b KEYNOTE-942/mRNA-4157-P201 study (NCT03897881) builds on the primary analysis conducted at approximately two years of follow up, as well as a subsequent analysis at three years of follow up. The safety profile of intismeran autogene, in combination with KEYTRUDA in the study, remains consistent with that previously reported. 

“For many patients with stage III/IV melanoma, there is a significant risk of recurrence following surgery. As such, demonstrating the longer-term potential of intismeran autogene and KEYTRUDA to reduce the risk of recurrence for certain patients with melanoma is a meaningful milestone. These five-year follow up data are encouraging and we look forward to late-stage data from the INTerpath clinical development programme with Moderna, across a range of tumour types where significant unmet needs remain,” said Dr Marjorie Green, Senior Vice President and Head of Oncology—Global Clinical Development, Merck Research Laboratories.

In collaboration with Merck, the phase III clinical trial for adjuvant melanoma (INTerpath-001, NCT05933577) is fully enrolled. Two Non-Small Cell Lung Cancer (NSCLC) phase III studies, evaluating adjuvant treatment in patients with completely resected NSCLC and evaluating adjuvant treatment for patients with resectable NSCLC after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy, are enrolling. The randomised phase II study for adjuvant renal cell carcinoma is fully enrolled. Randomised phase II studies for patients with resected muscle invasive and resected non-muscle invasive bladder cancer are enrolling, a phase II study of first-line treatment for patients with metastatic melanoma and a phase II study of first-line treatment for patients with metastatic squamous NSCLC are also enrolling.