Pfizer and Merck & Co. said today they will expand their joint research into combinations of their cancer treatments with a Phase Ib clinical study set to start next year in patients with anaplastic lymphoma kinase (ALK)-positive advanced or metastatic non-small cell lung cancer (NSCLC).
Financial terms were not disclosed for the companies’ latest collaboration, which will combine Pfizer’s Xalkori® (crizotinib) with Merck’s investigational drug pembrolizumab (MK-3475). Pfizer will conduct the multi-center, open-label clinical study, the latest in a string of combination cancer therapy studies by the pharma giants.
Xalkori is a kinase inhibitor indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. Pembrolizumab is an investigational, humanized, monoclonal antibody designed to reactivate anti-tumor immunity by targeting the PD-1 protein.
Pembrolizumab is designed to work through a dual ligand blockade of the PD-1 pathway, inhibiting the interaction of PD-1 on T cells with its ligands PD-L1 and PD-L2. Just yesterday, Reuters reported that the FDA is “likely to approve” pembrolizumab as a treatment for melanoma “within coming weeks” and well ahead of its Oct. 28 PDUFA target decision date, citing three unnamed “sources familiar with the situation.” The agency declined comment, citing its policy of not discussing the status of applications.
A melanoma indication would position pembrolizumab as Merck’s alternative to Bristol-Myers Squibb (BMS)’s already-marketed cancer immunotherapy Yervoy (ipilimumab). BMS and Merck & Co. are among drug developers scrambling to develop drugs targeting PD-1 or its complement, PD-L1.
“Evidence from early studies of pembrolizumab monotherapy together with Xalkori’s proven targeted therapeutic approach provides the scientific rationale for evaluating this combination for the treatment of lung cancer,” Eric Rubin, M.D., vp, Oncology, Merck Research Laboratories, said in a statement. “Understanding the effects of combining one drug, Xalkori, which inhibits an abnormally activated enzyme in patients with ALK-positive metastatic lung cancer, with the investigational drug, pembrolizumab, which harnesses the body’s immune system to fight cancer, is vital if we are to continue to advance the care of lung cancer patients.”
Back in February, both companies disclosed plans to launch a pair of cancer combination therapy studies. One will evaluate the safety and efficacy of Merck’s pembrolizumab with Pfizer’s small molecule kinase inhibitor Inlyta® (axitinib) in patients with renal cell carcinoma. The other will assess pembrolizumab plus Pfizer’s PF-05082566 (PF-2566), an investigational immuno-oncology agent that targets the human 4-1BB receptor, in multiple cancer types.
Pfizer agreed to conduct both studies, which are expected to begin enrolling their first patients by the end of this year.
The studies are among four connected with Pembrolizumab that are not yet recruiting patients; another 11 clinical studies are carrying out recruiting, while another study will provide expanded access to the Merck experimental drug for metastatic melanoma patients who have failed standard-of-care therapy including Yervoy, according to ClinicalTrials.gov.
Pembrolizumab is now under evaluation across more than 30 types of cancers, both alone and in combination with other drugs. That includes prostate cancer, where yesterday Merck and Advaxis said they will launch a Phase I/II study that will evaulate the safety and efficacy of pembrolizumab with Advaxis’ Lm-LLO cancer immunotherapy, ADXS-PSA.
By the end of 2014, the pembrolizumab development program is expected to grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.
Pfizer is one of several companies with which Merck is engaged in clinical collaborations for Pembrolizumab; others include Amgen, GlaxoSmithKline, and Incyte.