| Abstract: |
Background and objective: Initial results from the KEYNOTE-B61 trial demonstrated that pembrolizumab combined with lenvatinib has promising antitumor activity in previously untreated advanced non–clear-cell renal cell carcinoma (nccRCC). We report updated efficacy and safety results after nearly 2 yr of follow-up. Methods: The single-arm, multicenter, phase 2 KEYNOTE-B61 trial enrolled patients aged ≥18 yr with previously untreated advanced nccRCC. All participants received pembrolizumab 400 mg intravenously every 6 wk (up to 18 cycles, approx. 2 yr) plus lenvatinib 20 mg orally once daily. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1 as assessed on blinded independent central review. Duration of response (DOR) and safety were secondary endpoints. Key findings and limitations: A total of 158 patients received at least one dose of study treatment. Median follow-up was 22.8 mo (range 16.6–27.6). The ORR was 51% (95% confidence interval 43–59); 13 patients (8.2%) had a confirmed complete response and 67 (42%) had a confirmed partial response. In the subgroup with a confirmed response, median DOR was 19.5 mo (range 1.5+ to 23.5+). ORR was generally consistent across subgroups, including histologic subtypes (34–67%) and the presence of sarcomatoid features (47%). Grade 3 or 4 treatment-related adverse events were reported for 92 patients (58%). No deaths due to treatment-related adverse events occurred. Conclusion and clinical implications: After approximately 2 yr of follow-up, pembrolizumab plus lenvatinib showed durable antitumor activity in KEYNOTE-B61, with no new safety signals. These results support pembrolizumab + lenvatinib as a first-line treatment option for advanced nccRCC. © 2025 |
