Merck & Co. and Plexxikon Inc., a member of Daiichi Sankyo Group, have formed a collaborative clinical trial that will evaluate the combination of PLX3397, Plexxikon's investigational CSF-1R inhibitor, and Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, which provides the potential for a double blockade of cancer-induced immune suppression. The Phase I/II trial will enroll patients with advanced melanoma and multiple other solid tumors with the goal of determining the safety and tolerability of the combination therapy. The trial is expected to begin enrollment by mid-year.

PLX3397 is an oral small molecule that potently and selectively inhibits CSF-1R, KIT, and mutant FLT3 kinases. CSF1R and KIT regulate key components of both the tumor and its microenvironment (macrophages, osteoclasts, mast cells). In addition to melanoma and other solid tumors to be studied in this collaborative trial, PLX3397 is being evaluated in several other clinical indications, including tenosynovial giant cell tumor (TGCT), historically called pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), breast cancer and glioblastoma.

Keytruda (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merck has a broad clinical development program for Ketruda with more than 85 clinical trials across more than 30 tumor types and over 14,000 patients, both as a monotherapy and in combination with other therapies.

Source: Merck & Co.