WHITEHOUSE STATION, N.J.—Merck—also known as MSD outside the United States and Canada—has announced the signing of three separate clinical collaboration agreements, through subsidiaries, with Amgen Inc., Incyte Corporation and Pfizer Inc. for the evaluation of novel combination regimens with MK-3475, an investigational anti-PD-1 immunotherapy from Merck. No financial terms for the agreements were 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,” Dr. Roger M. Perlmutter, president of Merck Research Laboratories, said in a news release announcing the agreements. “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.”
Merck will work with Amgen to evaluate MK-3475 in combination with talimogene laherparepvec, Amgen’s investigational oncolytic immunotherapy, in a Phase 2/3 study in patients with previously untreated advanced melanoma. Talimogene laherparepvec is designed to selectively replicate within tumor tissue, causing lytic cell death, and engender a systemic anti-tumor immune response. The compound is also designed to express granulocyte-macrophage colony-stimulating factor, a white blood cell growth factor that can help activate the immune system.
“Talimogene laherparepvec has shown encouraging Phase 3 clinical results as a monotherapy in patients with metastatic melanoma,” David D. Chang, M.D., Ph.D., vice president of Global Development at Amgen, commented in a statement. “We look forward to working with Merck on this collaboration to evaluate the potential of these two novel immunotherapies to improve clinical outcomes for patients.”
Incyte and Merck will work together on a randomized, double-blind, placebo-controlled Phase 1/2 study to determine the safety and efficacy of a regiment consisting of MK-3475 and Incyte’s investigational immunotherapy agent, INCB24360, an indoleamine 2, 3-dioxygenase (IDO) inhibitor, in patients with previously treated metastatic and recurrent non-small cell lung cancer, as well as other advanced or metastatic cancers.
In the third collaboration, Merck will begin Phase 1/2 clinical studies with Pfizer to evaluate the safety and efficacy of combining MK-3475 with Pfizer’s small-molecule kinase inhibitor axitinib (INLYTA) in patients with renal cell carcinoma. They will also separately evaluate MK-3475 with PF-05082566 (PF-2566), an investigational immuno-oncology agent that targets the human 4-1BB receptor, as a treatment against multiple cancer types.
“There has been notable progress in the cancer immunotherapy field over the last year, with new clinical data showing promising efficacy and tolerability for emerging therapies – particularly those that target the PD-1 pathway,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. “These investigational therapies, which harness the body’s immune system to treat disease, may hold the greatest potential for patients with cancer when used in combination with other immuno-oncology agents, like PF-2566, to amplify anti-tumor immune responses, or with targeted agents, like axitinib, to optimize their effectiveness. We are pleased to collaborate with Merck to study a diverse group of our anti-cancer agents in combination with MK-3475, with the goal of identifying more efficacious treatment options for patients.”
Merck will also begin a Phase 1 “signal finding” study to determine the safety and efficacy of MK-3475 monotherapy in 20 different PD-L1-positive solid tumor types.
Many tumors evade the immune system via a mechanism that exploits the PD-1 inhibitory checkpoint, and MK-3475 is designed to selectively achieve dual ligand blockade of the PD-1 protein, thereby enabling activation of T cells and restoring the immune system’s ability to recognize and target cancer cells. The compound is under evaluation in 13 clinical trials in more than 30 cancer types, 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, among others.
