A combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) worked better than standard Sutent (sunitinib) in improving survival outcomes among adults with untreated advanced renal cell carcinoma (RCC) — the most common type of kidney cancer in adults — according to top-line data from a Phase 3 clinical trial.
Of note, Afinitor already is approved for advanced RCC following anti-angiogenic therapy, or medications that block the formation of new blood vessels, which are essential for tumor growth and survival.
“The results from CLEAR (Study 307)/KEYNOTE-581 support the potential use of Keytruda plus Lenvima for the first-line treatment of advanced RCC,” Takashi Owa, PhD, vice president, chief of medicine creation and chief discovery officer of the oncology business group at Eisai, said in a press release.
“These data also support the potential first-line use of Lenvima plus [Afinitor],” Owa added, noting that “these findings energize our efforts as we continue to advance our understanding and address the unmet needs of patients with difficult-to-treat cancers.”
Eisai and Merck (known as MSD outside North America), Keytruda’s developer, plan to present detailed trial results at an upcoming medical meeting. The companies also will discuss the study findings with regulatory authorities worldwide as they prepare to file applications for the Keytruda-Lenvima combo as a first-line treatment for advanced RCC.
An immune checkpoint inhibitor, Keytruda works by preventing an immune evasion mechanism involving the interaction between PD-L1 in cancer cells and the PD-1 receptor in T-cells — immune cells involved in the fight against cancer. By blocking this interaction, the therapy boosts anti-cancer responses and promotes cancer cell death.
Lenvima is an orally available small molecule that works by blocking kinases, or enzymes associated with blood vessel formation, tumor growth, and progression.
The Keytruda-Lenvima combo also received breakthrough therapy designation in the U.S. for the treatment of advanced RCC. That designation helps expedite the development and review of new medications that show improvement over available therapies in treating serious health conditions.
The ongoing KEYNOTE-581 Phase 3 trial (NCT02811861) is evaluating the safety and effectiveness of first-line treatment with Lenvima, in combination with either Keytruda or Afinitor, against standard treatment with Sutent in about 1,000 adults with advanced RCC.
Participants — with favorable, intermediate, and poor prognoses — were randomly assigned to receive one of three treatment regimens: 18 mg of Lenvima with 5 mg of Afinitor, once daily; 20 mg of Lenvima once-a-day in combination with 200 mg of Keytruda every three weeks; or 50 mg of Sutent once daily on a regimen of four weeks on treatment, followed by two weeks off treatment.
Lenvima, Afinitor, and Sutent are all given orally, while Keytruda is administered directly into the bloodstream (intravenously).
The trial’s main goal was to assess whether either combination therapy was superior to standard treatment at prolonging patients’ progression-free survival, or the time they lived without signs of disease progression. Secondary goals included overall survival, response rates, and safety measures.
Top-line results showed that participants treated with the Keytruda-Lenvima combo lived significantly longer and had greater progression-free survival than those given standard therapy with Sutent.
The Lenvima-Afinitor combination therapy also was significantly superior to Sutent at delaying disease progression. Both combos resulted in significantly better treatment responses than the standard Sutent treatment.
Based on these significant and clinically meaningful improvements, both combination therapies were found to meet the trial’s main goal and most of the secondary efficacy goals.
The safety profiles of both the Keytruda-Lenvima and Lenvima-Afinitor combos were consistent with those reported in previous trials.
“The results for Keytruda plus Lenvima versus [Sutent], 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, ” said Gregory Lubiniecki, MD, associate vice president of Merck Research Laboratories’ oncology clinical research.
“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,” Lubiniecki added.
Together, the companies are studying the Keytruda-Lenvima combo through their collaborative LEAP (LEnvatinib And Pembrolizumab) clinical program, which spans 19 trials in 13 different tumor types.