KEY TAKEAWAYS
- The INTerpath-004 phase 2 trial aimed to assess the safety and efficacy of pembro + V940 (mRNA-4157) or placebo in pts with RCC post-nephrectomy.
- The primary endpoint was to calculate DFS.
- The AEs will be monitored throughout, efficacy and safety assessed, and recruitment is ongoing.
Pembrolizumab (Pembro), PD-1 inhibitor is an approved monotherapy agent for the adjuvant treatment of patients (pts) with renal cell carcinoma (RCC) having an increased risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions based on results from the phase 3 KEYNOTE-564 trial.
Novel adjuvant strategies could provide further clinical implications in combinative settings. V940 (mRNA-4157) is a personaized neo-antigen therapy whihc is hypothesized to enhance the antitumor activity of T-cells and incline the pembro activity. Pembro + V940 demonstrated improved clinical outcomes for stage III/IV melanoma vs pembro alone in the phase 2b KEYNOTE-942 study.
Toni K Choueiri and the team aimed to evaluate the efficacy and safety of adjuvant pembro + V940 (mRNA-4157) or placebo in pts with RCC who have undergone nephrectomy.
Patient inclusion criteria is histologically or cytologically confirmed RCC with clear cell or papillary histology (intermediate-high risk [pT2 Gr4, N0, M0 or pT3 Gr3/4, N0, M0], high-risk [pT4, N0, M0 or pT any stage, N1, M0], or M1 NED [solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy or ≤2 years from nephrectomy]) with or without sarcomatoid features.
Additionally, included pts must be tumor-free as assessed by the investigator and have undergone nephrectomy and/or metastasectomy ≤12 weeks before randomization. Also, enrolled pts must not have previously received systemic therapy ≤4 weeks or radiotherapy ≤2 weeks before randomization.
About 272 pts will be randomly assigned 1:1 for intravenous administration of pembro (400 mg) every 6 weeks for up to 9 cycles in combination with either V940 (1 mg) or placebo via intramuscular route every 3 weeks for up to 9 doses or treatment discontinuation due to unacceptable toxicity, disease recurrence, patient withdrawal, or investigator decision.
Further sample stratification and randomization will be performed by histology (clear cell vs papillary) and disease risk (intermediate-high vs high vs M1 NED). Imaging assessments (computed tomography or magnetic resonance imagery) will be performed at interval of 12 weeks through year 2, every 16 weeks in years 3-5, and every 24 weeks in year 6 and beyond.
The primary endpoint of the study is to record the disease-free survival (DFS) by investigator assessment. Secondary endpoints include distant metastasis-free survival, overall survival (OS), and safety parameters including adverse events (AEs), laboratory test results, and vital signs.
Throughout monitoring of the AEs will be included in the planned study and for 30 days after the last dose of treatment (90 for serious AEs) which will be scaled as per the National Cancer Institute Common Terminology Criteria for AEs, version 5.0. Efficacy assessment will be performed in all randomly assigned pts, and safety will be evaluated in all pts who received ≥1 dose of study intervention while there is continuous recruitment ongoing.
The trial was sponsored by Merck Sharp & Dohme LLC.
Source: https://kcrs.kidneycan.org/wp-content/uploads/2024/06/KCRS24-Abstract-Book-6.27.24.pdf
Clinical Trial: https://clinicaltrials.gov/study/NCT06307431
Choueiri TK, Powles T, Braun D, et al. (2024). “INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA4157) or placebo in the adjuvant treatment of renal cell carcinoma.” Presented at KCRS 2024, (Abstract 45).
