European Commission Approves KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) as First-Line Treatment for Adult Patients With Advanced Renal Cell Carcinoma

Approval Based on Results From CLEAR/KEYNOTE-581 Trial Demonstrating KEYTRUDA Plus LENVIMA Significantly Reduced the Risk of Disease Progression or Death by 61%, With a Median Progression-Free Survival of Nearly Two Years Versus Nine Months for Sunitinib


San Francisco, CA (UroToday.com) -- Merck, known as MSD outside the United States and Canada, and Eisai announced that the European Commission has approved the combination of KEYTRUDA, Merck’s anti-PD-1 therapy, plus LENVIMA (KISPLYX® in the European Union [EU] for the treatment of advanced renal cell carcinoma [RCC]), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, for the first-line treatment of adult patients with advanced RCC.


The approval for advanced RCC is based on results from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial, in which KEYTRUDA plus LENVIMA demonstrated statistically significant improvements versus sunitinib in the efficacy outcome measures of progression-free survival (PFS), reducing the risk of disease progression or death by 61% (HR=0.39 [95% CI, 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib, and overall survival (OS), reducing the risk of death by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=0.0049) versus sunitinib. Median OS was not reached at the time of analysis in either study arm. The objective response rate (ORR) was 71% (95% CI, 66-76) for patients treated with KEYTRUDA plus LENVIMA (n=355) versus 36% (95% CI, 31-41) for patients treated with sunitinib (n=357; p<0.0001). Patients treated with KEYTRUDA plus LENVIMA achieved a complete response (CR) rate of 16% and partial response (PR) rate of 55% versus a CR rate of 4% and a PR rate of 32% for patients treated with sunitinib.

“A key focus of our collaboration with Eisai is to advance our clinical development program to evaluate the potential of KEYTRUDA plus LENVIMA to improve responses across different types of cancer, including renal cell carcinoma,” said Dr. Gregory Lubiniecki, Vice President, Clinical Research, Merck Research Laboratories. “Today’s approval of KEYTRUDA plus LENVIMA brings a new treatment option to patients with advanced renal cell carcinoma in Europe, and further validates our efforts to research this promising combination of an immunotherapy and tyrosine kinase inhibitor for some of the most difficult-to-treat cancers.”
“Renal cell carcinoma is the most common type of kidney cancer in both men and women, marking the significance of the European approval for the KEYTRUDA plus LENVIMA combination,” said Corina Dutcus, M.D., Vice President, Clinical Research, Oncology Business Group at Eisai Inc. “We remain committed to continuing to explore this combination therapy with the goal of improving care for people living with cancer. The participation of many patients, families, and healthcare providers made this approval possible, for which we are very grateful.”

The safety of KEYTRUDA in combination LENVIMA was evaluated in 497 patients with advanced RCC. The most frequently reported adverse reactions were diarrhea (62%), hypertension (52%), fatigue (47%), hypothyroidism (45%), decreased appetite (42%), nausea (40%), stomatitis (37%), proteinuria (33%), dysphonia (33%) and arthralgia (32%).

This approval allows marketing of KEYTRUDA plus LENVIMA in all 27 EU member states plus Iceland, Liechtenstein, Norway, and Northern Ireland. KEYTRUDA plus LENVIMA is now approved by the European Commission for two different types of cancer: for the first-line treatment of adult patients with advanced renal cell carcinoma and for advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation.


Source: Anon, 2021. European Commission approves Keytruda® (PEMBROLIZUMAB) plus LENVIMA® (lenvatinib) as first-line treatment for adult patients with advanced renal cell carcinoma. Merck.com.