Date: 2017-03-31

Type of information: Clinical research agreement

Compound: epacadostat and Keytruda® (pembrolizumab)

Company: Incyte (USA - DE) Merck&Co (USA - NJ)

Therapeutic area: Cancer - Oncology

Type agreement: clinical research

Action mechanism: enzyme inhibitor/immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer types. Keytruda® (pembrolizumab - MK-3475) is an highly selective monoclonal anti-PD-1 antibody 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, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It has received a Breakthrough Therapy designation for advanced melanoma, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. In November 2015, the FDA has granted Breakthrough Therapy Designation to Keytruda® for the treatment of patients with microsatellite instability high (MSI-H)metastatic colorectal cancer.

Disease: advanced or metastatic melanoma, non-small cell lung cancer (NSCLC), bladder cancer, renal cell carcinoma (RCC), squamous cell carcinoma of the head and neck (SCCHN)

Details: • On October 13, 2015, Incyte and Merck&Co announced the expansion of the companies' ongoing clinical collaboration to include a Phase 3 study evaluating the combination of epacadostat, Incyte's investigational selective IDO1 inhibitor, with Keytruda® (pembrolizumab), Merck's anti-PD-1 therapy, as first-line treatment for patients with advanced or metastatic melanoma. The Phase 3 study, which is expected to begin in the first half of 2016, will be co-funded by Incyte and Merck&Co. Under the terms of the agreement Incyte and Merck have also agreed, for a period of two years, not to initiate new pivotal studies of an IDO1 inhibitor in combination with a PD-1/PD-L1 antagonist as first-line therapy in advanced or metastatic melanoma with any third party. During this time, the companies will each offer the other the opportunity to collaborate on any new pivotal study involving an IDO1 inhibitor in combination with a PD-1/PD-L1 antagonist for types of melanoma and lines of therapy outside of the current collaboration agreement. The agreement is between Incyte and certain subsidiaries and Merck through its subsidiaries.

Financial terms:

Latest news:

  • • On March 31, 2017, Incyte and Merck&Co announced additional details of their clinical development program investigating the combination of epacadostat with Keytruda® (pembrolizumab), in patients across five tumor types: metastatic melanoma, non-small cell lung cancer (NSCLC), bladder cancer, renal cell carcinoma (RCC), and squamous cell carcinoma of the head and neck (SCCHN).The expanded collaboration now includes seven pivotal studies:
  • - a Phase 3 study in metastatic melanoma (trial underway);
  • - two Phase 3 studies in first-line NSCLC, including both PD-L1 high-expressing and PD-L1 unselected populations;
  • - two Phase 3 studies in bladder cancer, including one in first-line bladder cancer and one in second-line bladder cancer;
  • - a Phase 3 study in first-line RCC; and
  • - a Phase 3 study in first-line SCCHN.
  • Incyte and Merck&Co will share responsibilities for funding these pivotal studies, and Merck&Co will be responsible for conducting the trials.

Is general: Yes