ASCO 2023: First-Line Lenvatinib + Pembrolizumab Treatment Across Non-Clear Cell Renal Cell Carcinomas: Results of the Phase 2 KEYNOTE-B61 Study

( Dr. Chung-Han Lee Lee presents the results of a phase 2 KEYNOTE-B61 study, which evaluates first line lenvatinib + pembrolizumab treatment across non-clear cell renal cell carcinomas.

Lenvatinib (Lenva) and pembrolizumab (Pembro) combination therapy is already an established first line treatment for advanced clear cell renal cell carcinoma. However, as we have seen before these same results cannot always be expected for patients with non clear cell histology.

Non-clear cell histology RCC is a heterogeneous group of aggressive tumors with limited treatment options. Therapeutic options have been largely derived from clear cell RCC studies.

Initial results of a phase II single-arm KEYNOTE-B61 trial have previously been reported and have demonstrated anti-tumor activity of this combination in patients advanced non-clear cell RCC. Objective response rate was 47.6% and disease control rate was 79%.

In that initial cohort, 82 patients were included. Now, with the complete cohort of 158 patients enrolled and extended follow-up, Dr. Lee presents updated results.

The original study design is seen below:


It should be noted that for the context of this study, histology was assessed by the investigator - but the central review is eventually planned.

The flow of patients is seen below:


92 patients remain on treatment of the 155 patients enrolled.

Baseline characteristics are seen below:


The majority of patients had papillary RCC (58.8%), while 18% had chromophobe. The rest for unclassified, translocation, or other. only 12% of patients had sarcomatoid features.

Median follow-up was 14.9 mo (range 8.7-19.7).

Looking at updated outcomes:


  • ORR remains high at 49%
  • DCR remained high at 82%

The change in size of the primary tumor was also significant, as noted below:

KEYNOTE-B61 ASCO 2023.jpg

As initially reported, outcomes varied by histologic subtype:


Chromophobe RCC had the lowest ORR, while the remaining subtypes had a better response.

KM curves for PFS and OS are seen below:

ASCO 2023 KEYNOTE-B61.jpg

Broken down by IMDC risk group:

  • Favorable risk group, ORR was 51% (95% CI, 39-64) and DCR was 87% (95% CI, 77-94).
  • IMDC intermediate/poor risk group, ORR was 48% (95% CI, 37-59) and DCR was 78% (95% CI, 68-86).

In terms of safety and tolerability, treatment-related AEs (TRAEs) occurred in 149 pts (94%) and were consistent with results from other studies. No new signals were noted. Overall, 17 pts (11%) discontinued pembro, 14 (9%) discontinued lenva, and 5 (3%) discontinued both drugs because of TRAEs. No deaths occurred because of TRAEs.

In this really important trial, combination Lenva+pembro continues to demonstrate excellent antitumor activity with no new safety signals. These results will likely support using this combination as first line treatment for patients with non clear cell RCC regardless of Histology. However, we should note that the effect size was much less in patients with chromophobe RCC.

Presented by: Chung-Han Lee, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis, @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.