Merck, Moderna Launch Phase III Trial of V940 in Combination with Keytruda for Resectable Non-Small Cell Lung Cancer

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Merck and Moderna announced the beginning of the Phase III INTerpath-009 trial for V940 (mRNA-4157) in combination with Keytruda (pembrolizumab) as an adjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after neoadjuvant Keytruda plus chemotherapy. According to Moderna, global recruitment has begun, with the first patients being recruited in Canada.¹

“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,” said Marjorie Green, SVP, head, oncology, global clinical development, Merck Research Laboratories, in a press release. “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.”

The global, randomized, double-blind INTerpath-009 trial enrolled 680 patients over 18 years of age. After surgical resection, participants are expected will be randomly assigned in a 1:1 ratio to receive either 1 mg of V940, an investigational individualized neoantigen therapy (INT), every three weeks for up to nine doses and 400 mg of Keytruda every six weeks up to seven cycles, or placebo and Keytruda. The primary endpoint of the trial is disease-free survival, defined as the time from randomization to any recurrence, occurrence of new primary NSCLC as assessed by the investigator, or death due to any cause, whichever occurs first. Secondary endpoints include overall survival, distant metastasis-free survival (DMFS), disease-free survival, lung cancer-specific survival, safety, and quality of life.¹

Back in June, Moderna and Merck announced positive results from the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial, which evaluated V940 in combination with Keytruda in patients with high-risk melanoma following complete resection. The combination therapy demonstrated sustained benefits in recurrence-free survival and DMFS.^2,3 Also in 2024, investigators initiated a two-part Phase II/III randomized clinical trial evaluating the combination therapy as neoadjuvant and adjuvant treatment in patients with resectable locally advanced Stage II-IV (M0) cutaneous squamous cell carcinoma. Moderna and Merck also initiated two Phase II trials evaluating the combination in patients with intermediate-high-risk, high-risk, or M1 no evidence of disease renal cell carcinoma, and high-risk muscle-invasive urothelial carcinoma post-radical resection.¹

According to the American Cancer Society, NSCLC comprises 85% of all lung cancers. Lung cancer overall is the second most common cancer in the United States for both men and women. By the end of 2024, it is estimated that there will be around 234,580 new cases of lung cancer and approximately 125,070 deaths. In most cases, patients are first diagnosed over 65 years of age, with a median diagnosis age of 70 years; however, a minority of patients have been diagnosed under 45 years of age.⁴

“We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC,” said Kyle Holen, MD, SVP, head, development, therapeutics and oncology, Moderna, in the press release. “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.”

References

1. Merck and Moderna Initiate Phase 3 Trial Evaluating Adjuvant V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab) After Neoadjuvant KEYTRUDA and Chemotherapy in Patients With Certain Types of Non-Small Cell Lung Cancer (NSCLC). Moderna. October 28, 2024. Accessed October 28, 2024. https://investors.modernatx.com/news/news-details/2024/Merck-and-Moderna-Initiate-Phase-3-Trial-Evaluating-Adjuvant-V940-mRNA-4157-in-Combination-with-KEYTRUDA-pembrolizumab-After-Neoadjuvant-KEYTRUDA-and-Chemotherapy-in-Patients-With-Certain-Types-of-Non-Small-Cell-Lung-Cancer-NSCLC/default.aspx

2. Moderna, Merck Present Promising Trial Data for a Combination of V940 with Keytruda for the Treatment of High-Risk Melanoma Following Complete Resection. PharmExec. June 4, 2024. Accessed October 28, 2024. https://www.pharmexec.com/view/moderna-merck-present-promising-trial-data-for-a-combination-of-v940-with-keytruda-for-the-treatment-of-high-risk-melanoma-following-complete-resection

3. Moderna & Merck Announce 3-Year Data For mRNA-4157 (V940) in Combination With KEYTRUDA(R) (pembrolizumab) Demonstrated Sustained Improvement in Recurrence-Free Survival & Distant Metastasis-Free Survival Versus KEYTRUDA in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection. Moderna. June 3, 2024. Accessed October 28, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna--Merck-Announce-3-Year-Data-For-mRNA-4157-V940-in-Combination-With-KEYTRUDAR-pembrolizumab-Demonstrated-Sustained-Improvement-in-Recurrence-Free-Survival--Distant-Metastasis-Free-Survival-Versus-KEYTRUDA-in-Patients-With-High-Risk-Stage-IIIIV/default.aspx

4. Key Statistics for Lung Cancer. American Cancer Society. Accessed October 28, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=Most%20lung%20cancer%20statistics%20include,breast%2C%20and%20prostate%20cancers%20combined.