Pembrolizumab Plus Lenvatinib Combo Approved for Treatment of First-Line Advanced RCC

The combination of pembrolizumab plus lenvatinib received approval by the FDA in the first-line setting for patients with advanced renal cell carcinoma following the results of the phase 3 CLEAR trial.

The FDA has approved the use of first-line pembrolizumab (Keytruda) plus lenvatinib (Lenvima) for the treatment of patients with advanced renal cell carcinoma (RCC), according to a press release from Merck.

The approval was based on findings from the phase 3 CLEAR (Study 307)/KEYNOTE-581 trial (NCT02811861) in which the agent yielded notable improvements in survival and response rate vs sunitinib. Data from the trial indicated that, in terms of progression-free survival (PFS), the combination reduced the risk of disease progression of death by 61% vs the single agent treatment (HR, 0.39; 95% CI, 0.32-0.49; P <.0001). Investigators reported a median PFS of 23.9 months with the pembrolizumab/lenvatinib combination compared with 9.2 months in the sunitinib arm. In terms of overall survival (OS), the combination reduced the risk of mortality by 34% compared with sunitinib (HR, 0.66; 95% CI, 0.49-0.88; P = .0049).

The combination also yielded a confirmed overall response rate (ORR) of 71% (95% CI, 66%-76%), including a complete response (CR) rate of 16% and a partial response (PR) rate of 55%. Comparatively, the sunitinib cohort had an ORR of 36% (95% CI, 31%-41%), including a CR rate of 4% and a PR rate of 32%.

“This FDA approval is truly significant for the advanced renal cell carcinoma community. The CLEAR/KEYNOTE-581 trial shows treatment with Keytruda plus Lenvima resulted in superior outcomes across progression-free survival, overall survival, and objective response rate versus sunitinib in patients with advanced renal cell carcinoma,” Takashi Owa, chief medicine creation and chief discovery officer of the Oncology Business Group at Eisai, said in a press release. “This milestone is a testament to our dedication to developing new therapeutic options for people living with advanced cancers, which is fueled by our passion for aiming to improve cancer care for patients, and amplified by the teamwork resulting from our collaboration with Merck.”

A number of severe or fatal immune-mediated adverse effects (AE) can occur after receiving treatment with pembrolizumab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions. Moreover, AEs that can occur with lenvatinib include hypertension, cardiac dysfunction, arterial thromboembolic events, hepatoxicity, and renal failure or impairment.

“This FDA approval reinforces the potential of Keytruda plus Lenvima, which is now approved for 2 different types of cancer. In the study, Keytruda plus Lenvima demonstrated a survival benefit for patients with advanced renal cell carcinoma, supporting the importance of this combination as a new first-line treatment option for these patients,” Gregory Lubiniecki, vice president, oncology clinical research at Merck Research Laboratories, said in a press release. “At Merck, we are focused on delivering meaningful innovations that extend the lives of people with cancer. We are proud to see how our collaboration with Eisai can now help to improve survival outcomes for patients with advanced renal cell carcinoma and are committed to further exploring Keytruda plus Lenvima in other difficult-to-treat cancers."

Previously, the immunotherapy/tyrosine kinase inhibitor combination was granted priority review by the FDA for this inidication. This approval comes ahead of the Prescription Drug User Fee Act (PDUFA) date of August 25, 2021 set by the agency.


FDA Approves Keytruda (pembrolizumab) Plus Lenvima (lenvatinib) Combination for First-Line Treatment of Adult Patients With Advanced Renal Cell Carcinoma (RCC). News release. Merck. August 11, 2021. Accessed August 11, 2021.

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