A Study of Adjuvant Intismeran Autogene (V940) and Pembrolizumab in Renal Cell Carcinoma (V940-004).

A Phase 2, Randomized, Double-blind, Clinical Study of V940 (mRNA-4157) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in the Adjuvant Treatment of Participants With Renal Cell Carcinoma (INTerpath-004).

The primary objective of the study is to compare intismeran autogene plus pembrolizumab to placebo plus pembrolizumab in participants with renal cell carcinoma (RCC) with respect to disease-free survival (DFS) as assessed by the investigator. The primary hypothesis is that intismeran autogene plus pembrolizumab is superior to placebo plus pembrolizumab with respect to DFS.

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell or papillary histology.
• Has intermediate-high-risk, high-risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading:
• Intermediate-high-risk RCC: pT2 Gr4, N0, M0; pT3 Gr3/4, N0, M0
• High-risk RCC: pT4, N0, M0; pT any stage, N1, M0
• M1 NED RCC participants who present not only with the primary kidney tumor, but also solid, isolated, soft tissue metastases that can be completely resected at 1 of the following: the time of nephrectomy (synchronous), or ≤2 years from nephrectomy (metachronous)
• Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants.
• Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and recovered from surgery and any post-operative complications before randomization.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.

Exclusion Criteria:

• Has had a major surgery other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization.
• Has residual thrombus post nephrectomy in the vena renalis or vena cava.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Received prior treatment with a cancer vaccine.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has a history of brain or bone metastatic lesions.
• Has severe hypersensitivity to study medication or any of the substances used to prepare the study medication.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• History of allogeneic tissue/solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications