Keytruda-Inlyta Combo Extends Survival in Advanced Renal Cell Carcinoma Patients, Phase 3 Trial Shows

Keytruda-Inlyta Combo Extends Survival in Advanced Renal Cell Carcinoma Patients, Phase 3 Trial Shows

A combination of Keytruda (pembrolizumab) and Inlyta (axitinib) significantly extended the lives of patients with advanced renal cell carcinoma (RCC) and delayed disease progression or death, according to a Phase 3 clinical trial.

The randomized trial, called KEYNOTE-426 (NCT02853331), examined the combination versus the standard of care Sutent (sunitinib) as a first-line treatment for advanced RCC patients. The combination also met its secondary objective of overall response rate, with more patients responding to it than to Sutent.

“Keytruda, in combination with the tyrosine kinase inhibitor Inlyta, resulted in significant and clinically meaningful improvements in overall survival, progression-free survival and objective response in this Phase 3 study,” Roger M. Perlmutter, president of Merck Research Laboratories, said in a press release.

“This marks the first time that combination treatment with an anti-PD-1 therapy has achieved the dual primary endpoints of overall survival and progression-free survival as first-line therapy in advanced renal cell carcinoma,” he said.

Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is an immune checkpoint inhibitor that unleashes the full power of immune cells into cancer cells. It blocks the interaction between the PD-1 molecule on immune cells and the PD-L1 protein in cancer cells, preventing cancer cells from escaping immune surveillance.

Inlyta, by Pfizer, is a protein kinase inhibitor that blocks signals that help cancer cells grow and replicate without control.

In a prior Phase 1b trial (NCT02133742), sponsored by Pfizer and Merck, researchers had already seen that a combination of Keytruda and Inlyta had promising anti-tumor activity, when given to untreated advanced RCC patients. In the open-label trial, 73% of patients experienced tumor reduction, including four complete responses and 34 partial responses. An additional eight patients achieved stable disease.

Based on those findings, Merck designed KEYNOTE-426 to determine if the combination outperformed the standard of care Sutent in these patients.

The study recruited 861 patients who were randomly assigned Keytruda, given into the vein every three weeks, in combination with oral Inlyta twice a day, or oral Sutent once a day. The study is now ongoing, with an estimated completion date in January 2020.

In addition to survival, progression-free survival, and overall response rates — all of which were met — the trial is also examining the duration of response, disease control rate, and safety as secondary measures.