Merck known as MSD outside the United States and Canada, has announced that the pivotal phase 3 KEYNOTE-040 trial investigating Keytruda (pembrolizumab), the company’s anti-PD-1 therapy, in previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) did not meet its pre-specified primary endpoint of overall survival (OS) (HR, 0.82 [95% CI, 0.67-1.01]; p = 0.03 [one-sided]). The safety profile observed in KEYNOTE-040 was consistent with that observed in previously reported studies of Keytruda; no new safety signals were identified.

In August 2016, the US Food and Drug Administration (FDA) approved Keytruda for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. The current indication remains unchanged and clinical trials continue, including KEYNOTE-048 (ClinicalTrials.gov, NCT02358031), a phase 3 clinical trial of Keytruda in the first-line treatment of recurrent or metastatic HNSCC.

“We are encouraged by the positive impact that Keytruda has had on many cancer patients, including those with previously treated recurrent or metastatic head and neck cancer, and we remain confident that Keytruda is an important therapy for this difficult-to-treat cancer,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We look forward to sharing the comprehensive data analysis from KEYNOTE-040 with the scientific community at an upcoming medical meeting.”

The Keytruda clinical development program includes more than 30 tumor types in more than 500 clinical trials, including more than 300 trials that combine Keytruda with other cancer treatments. Specific to head and neck cancer, Merck’s broad clinical development program encompasses multiple registration-enabling or supportive studies investigating Keytruda (pembrolizumab) as monotherapy and in combination with other cancer treatments across multiple lines of therapy.

KEYNOTE-040 is a randomized, multi-center, pivotal phase 3 study (ClinicalTrials.gov, NCT02252042) investigating Keytruda as a monotherapy versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic HNSCC. The primary endpoint is OS; secondary endpoints include progression-free survival (PFS) and overall response rate (ORR). The study, which opened in November 2014, enrolled 495 patients to receive Keytruda (200 mg fixed dose every three weeks) or investigator-choice chemotherapy (methotrexate [40 mg/m2 on Days 1, 8, and 15 of each 3-week cycle], docetaxel [75 mg/m2 on Day 1 of each 3-week cycle], or cetuximab [400 mg/m2 loading dose on Day 1 and 250 mg/m2 IV on Days 8 and 15 of Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and 15 of each subsequent 3-week cycle]). Patients enrolled in the study had been previously treated with 1-2 platinum-containing systemic regimens.

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumour cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Studies of Keytruda – from the largest immuno-oncology program in the industry with more than 500 trials – include a wide variety of cancers and treatment settings. The Keytruda (pembrolizumab) clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with Keytruda, including the exploration of several different biomarkers across a broad range of tumours.

Keytruda is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. Keytruda for injection is supplied in a 100 mg single-dose vial.