Merck & Co. Inc. has announced one expanded pact with Amgen and two new pacts with other companies for its anti-cancer drug, Keytruda (pembrolizumab), humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

The pacts involve the clinical development of Keytruda in additional cancer types. Keytruda is approved in the United States for treating unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Merck is advancing a broad clinical development program for Keytruda with more than 100 clinical trials across more than 30 tumor types and enrolling more than 16,000 patients, both as a monotherapy and in combination with other therapies.

In the first deal, Merck and Amgen expanded their collaboration to evaluate the efficacy and safety of talimogene laherparepvec, Amgen's investigational oncolytic immunotherapy, in combination with Merck’s Keytruda in a Phase 1 trial for treating metastatic squamous cell carcinoma of the head and neck (SCCHN). In addition, the companies announced that a global, randomized Phase III trial evaluating the combination in patients with regionally or distantly metastatic melanoma is being initiated. As previously announced, the compounds are being studied in a Phase I trial in this patient population. Both immunotherapies are designed to modulate the immune system. Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response against cancer cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.

Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body. Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

Merck also announced a collaboration with Tesaro Inc., an oncology-focused biopharmaceutical company to evaluate the combination of Tesaro’s niraparib plus Merck's anti-PD1 therapy, Keytruda (pembrolizumab), in a Phase I/II clinical trial. The trial is planned to evaluate the preliminary safety and efficacy of niraparib plus Keytruda in patients with triple negative breast cancer or ovarian cancer. This trial will be conducted by Tesaro and Merck, through a subsidiary, and is expected to begin by the end of 2015.

Niraparib is an oral, selective inhibitor of PARP-1 and PARP-2. PARP, or poly (ADP-ribose) polymerase, is a DNA repair protein that restores single strand DNA breaks. By inhibiting PARP, certain cancer cells may be rendered unable to repair DNA damage, which can lead to cell death. A Phase 1/2 monotherapy study of niraparib was completed in patients with advanced solid tumors. Two Phase III trials are currently ongoing to evaluate a single oral dose of niraparib as a maintenance therapy for patients with ovarian cancer and as a treatment for patients with BRCA-positive breast cancer. A Phase II study designed to evaluate niraparib as a treatment for patients with ovarian cancer who have received prior therapies is also ongoing.

Merck & Co. Inc. and NanoString Technologies, Inc., a provider of life science tools for translational research and molecular diagnostic products, have formed a clinical research collaboration to develop an assay that will optimize immune-related gene expression signatures and evaluate the potential to predict benefit from Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), in multiple tumor types. The collaboration will use NanoString's nCounter Analysis System to optimize gene expression signatures as part of the clinical development program for Keytruda.

Source: Merck (Amgen), Merck (NanoString), Merck (Tesaro)