Clinical Trials

Date: 2017-07-05

Type of information: Halting of the trial

phase: 3

Announcement: halting of the trial

Company: Merck&Co (USA - NJ)

Product: pembrolizumab (MK-3475)

Action mechanism: monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is an investigational, 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, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system. MK-3475 is currently being studied in three clinical trials for advanced melanoma including a Phase III trial of MK-3475 versus ipilimumab in ipilimumab-naïve advanced melanoma patients (PN 006). Enrollment is complete in the advanced melanoma cohorts in the company’s Phase IB trial (PN 001) and the Phase II trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide. In April 2013, MK-3475 has received a Breakthrough Therapy designation for advanced melanoma from the FDA. In October 2014, the FDA has gralso anted Breakthrough Therapy Designation to Keytruda® (pembrolizumab) 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. Keytruda® is the first approved drug that blocks the PD-1 cellular pathway. The Keytruda® clinical development program includes patients with more than 30 tumor types in more than 160 clinical trials, including more than 80 trials that combine Keytruda® with other cancer treatments. Registration-enabling trials of Keytruda® are currently enrolling patients in melanoma, NSCLC, head and neck cancer, bladder cancer, gastric cancer, colorectal cancer, esophageal cancer, breast cancer, Hodgkin lymphoma, multiple myeloma and other tumors, with further trials in planning for other cancers.

Disease: multiple myeloma

Therapeutic area: Cancer - Oncology

Country: Australia, Canada, France, Germany, Ireland, Israel, Italy, Japan, New Zealand, Norway, Russian Federation, South Africa, Spain, UK, USA

Trial details: The purpose of the KEYNOTE 185 study is to compare the efficacy of lenalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of lenalidomide and low dose dexamethasone without pembrolizumab in terms of progression-free survival (PFS) in participants with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT). (NCT02579863)

Latest news:

  • • On July 5, 2017, Merck&Co announced that the FDA has placed a clinical hold on KEYNOTE-183, KEYNOTE-185 and KEYNOTE-023, three combination studies of Keytruda® (pembrolizumab), in multiple myeloma. This decision follows a review of data by the Data Monitoring Committee in which more deaths were observed in the Keytruda® arms of KEYNOTE-183 and KEYNOTE-185 and which led to the pause in new patient enrollment, as announced on June 12, 2017. The FDA has determined that the data available at the present time indicate that the risks of Keytruda® plus pomalidomide or lenalidomide outweigh any potential benefit for patients with multiple myeloma. All patients enrolled in KEYNOTE-183 and KEYNOTE-185 and those in the Keytruda®/lenalidomide/dexamethasone cohort in KEYNOTE-023 will discontinue investigational treatment with Keytruda®.
  •  KEYNOTE-183 and KEYNOTE-185 have been placed on full clinical hold.
  • KEYNOTE-023 Cohort 1 has been placed on partial clinical hold. This cohort evaluated Keytruda® (pembrolizumab) in combination with lenalidomide and dexamethasone in patients who received prior anti-multiple myeloma treatment with an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide).
  • This clinical hold does not apply to other studies with Keytruda®.
  • • On October 16, 2015, a Phase 3 trial sponsored by Merck&Co was published on the NIH website for pembrolizumab and is currently recruiting participants.

Is general: Yes