Pembrolizumab plus lenvatinib improves survival in frontline kidney cancer

Findings from the phase 3 KEYNOTE-581/CLEAR trial (Study 307) showed that the combination improved overall survival, progression-free survival, and response versus sunitinib.

The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) improved overall survival (OS) versus sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC), according to findings from the phase 3 KEYNOTE-581/CLEAR trial (Study 307).1

The combination of the anti–PD-1 immunotherapy and the multikinase inhibitor also led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and response compared with sunitinib. The study also showed that combining lenvatinib with everolimus (Afinitor) significantly improved PFS and response versus sunitinib in frontline RCC.

Data from the trial have not yet been made available, with Merck (MSD) and Eisai, the developers of pembrolizumab and lenvatinib, respectively, planning to share the results at an upcoming medical meeting and discuss them with regulatory authorities in the United States and other countries.

“The results for Keytruda plus Lenvima versus sunitinib, which showed a statistically significant improvement in progression-free survival, overall survival and objective response rate, build on the growing scientific evidence that supports the investigation of Keytruda-based combinations for the first-line treatment of advanced renal cell carcinoma,” Gregory Lubiniecki, MD, associate vice president, Oncology Clinical Research, Merck Research Laboratories, stated in a press release.

“Merck and Eisai are committed to working together to continue to explore the potential of the Keytruda plus Lenvima combination, particularly in areas of great unmet need such as renal cell carcinoma,” added Lubiniecki.

The multicenter open-label phase 3 CLEAR trial (NCT02811861) randomized patients with advanced RCC to receive pembrolizumab/lenvatinib, lenvatinib/everolimus, or sunitinib. Overall, approximately 1050 patients were randomized, and the intent-to-treat population included patients across all risk groups. No new safety signals emerged compared to previously reported data for the study treatments.

Prior RCC results with pembrolizumab/lenvatinib

Previously reported data showed activity with pembrolizumab plus lenvatinib in patients with RCC who had prior therapy. Phase 2 data were shared during the 2020 ASCO Virtual meeting for 104 patients with metastatic clear cell RCC who had disease progression following immunotherapy with an anti–PD-1/PD-L1 treatment.2

The median patient age at baseline was 60 years (range, 36-82) and 75% of patients had prior nephrectomy. Seventy-seven percent of patients were male, 45% had an ECOG performance status of 0, and 55% had an ECOG performance status of 1. Regarding risk status, 36% were favorable, 42% were intermediate, and 22% were poor. PD-L1 status was positive for 42% of patients, negative for 41%, and not available for 16%.

The results showed that the ORR was 55%, comprised of all partial responses. An additional 36% of patients achieved stable disease. The median duration of response was 12 months. Five percent of patients had progressive disease.


1. KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Demonstrated Statistically Significant Improvement in Progression-Free Survival (PFS), Overall Survival (OS) and Objective Response Rate (ORR) Versus Sunitinib as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma. Posted online November 10, 2020. Accessed November 10, 2020.

2. Lee C-H, Shah AY, Hsieh JJ, et al. Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC). J Clin Oncol 38: 2020 (suppl; abstr 5008).

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