Pfizer, Amgen, and Incyte have announced a collaborative effort to study Merck's immunotherapy MK-3475 in combination with their own.

Several of the biggest drug companies in the world have announced a collaborative effort to make the most of Merck's anti–PD-1 antibody MK-3475 by studying it alongside treatments of their own.

Pfizer has agreed to test MK-3475 in combination with its monoclonal anti-CD137 antibody PF-2566, which it hopes will further amplify the immune response, and, separately, with the targeted kinase inhibitor axitinib (Inlyta), aimed at VEGF receptors 1, 2, and 3, to optimize effectiveness in renal cell carcinoma. Amgen will test the drug with its oncolytic virus talimogene laherparepvec (OncoVex) in patients with previously untreated advanced melanoma; and Incyte will test it alongside its immunotherapy agent INCB24360, an indoleamine 2,3-dioxygenase inhibitor, in patients with metastatic and recurrent non–small cell lung cancer, among others. All the studies are phase I/II.

Glenn Dranoff, MD, a cancer immunologist at Dana-Farber Cancer Institute (DFCI) and Harvard Medical School, both in Boston, MA, and co-leader of the Cancer Vaccine Center at DFCI, says there's convincing preclinical data to suggest that all of these combinations are worth trying.

Although Merck continues to test MK-3475 as a monotherapy against late-stage tumor types, there is little doubt in the industry that combination therapy is the way forward. Because tumors are adept at escaping the immune system, combination therapies have the potential “to elicit much stronger responses,” says Dranoff.

Competition in the cancer immunotherapy field is great, and companies are rushing to identify and market the best combinations first.

“Time is of the essence given the number of companies that have independent programs and the indication that immunotherapies are active across a range of tumor types,” adds Dranoff.

Like other immune therapies, MK-3475 combats a tumor's ability to evade the immune system. By blocking PD-1, it essentially releases a brake on the immune system, enabling the activation of T-cells to target the cancer.

David Mauro, MD, executive director of clinical oncology at Merck Research Laboratories in Upper Gwynedd, PA, says his company hopes that the testing will help expand MK-3475 into tumors where it hasn't worked as a monotherapy. Merck was less concerned, he says, about finding both parts of the combination in-house.

“What we wanted to do was pull together a portfolio of combinations that made sense regardless of whether they were internal compounds or with other companies,” explains Mauro.

Financial terms of the collaboration were not disclosed, but Mauro notes that it was surprisingly easy for the companies to reach mutually acceptable deals. “I've been in the business for a while, and I've never seen companies willing to work together so easily,” he says. “There's less the spirit of competitiveness and much greater spirit of collaboration.”

Mace Rothenberg, MD, senior vice president of clinical development and medical affairs of Pfizer in New York, NY, says the deal simply made sense.

“We are exploring opportunities to evaluate our assets in combinations where there is strong scientific rationale and in a variety of tumor types,” explains Rothenberg. “We are prioritizing these opportunities based on unmet need, insight into cancer genomics, promising preclinical data, and/or early signs of clinical activity.”

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