Merck has signed three separate clinical collaboration agreements, through subsidiaries, with Amgen, Incyte and Pfizer to evaluate novel combination regimens with MK-3475, Merck’s investigational anti-PD-1 immunotherapy. Financial terms have not been disclosed.
“Merck clinical scientists intend to explore the potential of our PD-1 inhibitor across a wide range of cancers, both as monotherapy and in combination,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “These new collaborations with Amgen, Incyte and Pfizer underscore our shared determination to evaluate treatment regimens with the potential to provide meaningful benefits to patients suffering from cancer.”
Pfizer and Merck will evaluate in phase I/II clinical studies the safety and efficacy of MK-3475 in combination with Pfizer’s small molecule kinase inhibitor axitinib (INLYTA) in patients with renal cell carcinoma, and separately MK-3475 plus PF-05082566 (PF-2566), an investigational immuno-oncology agent that targets the human 4-1BB receptor, in multiple cancer types.
Incyte and Merck will collaborate on a randomized, double-blind, placebo-controlled phase I/II study to evaluate the safety and efficacy of a regimen combining MK-3475 with Incyte’s investigational immunotherapy agent, INCB24360, an indoleamine 2, 3-dioxygenase (IDO) inhibitor, in patients with previously treated metastatic and recurrent NSCLC, among other advanced or metastatic cancers.
Amgen and Merck will evaluate MK-3475 in combination with Amgen’s investigational oncolytic immunotherapy talimogene laherparepvec in a phase I/II study in patients with previously untreated advanced melanoma.
Separately, Merck announced it will start a new phase I “signal finding” study to evaluate the safety and efficacy of MK-3475 monotherapy in 20 different PD-L1-positive solid tumor types that have not been studied previously.
Many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer, essentially by releasing a brake on the immune system.
MK-3475 is being studied in 13 clinical trials estimated to enroll more than 4,000 patients across more than 30 types of cancer including: bladder, colorectal, gastric, head and neck, melanoma, non-small and small cell lung, renal, pancreatic, prostate, triple negative and estrogen-receptor positive HER 2-negative breast, gynecologic and hematological malignancies. Additional trials, both as monotherapy and in combination with other cancer therapies, are planned.
Breakthrough Therapy designation for MK-3475 in advanced melanoma was granted by the FDA in April 2013. Merck announced in January the initiation of a rolling submission of a BLA for MK-3475 in advanced melanoma in the U.S. The company expects to complete the submission in the first half of 2014.