A Phase 1/2 clinical trial evaluating the investigational drugs avelumab, a PD-L1 inhibitor, and defactinib, a FAK inhibitor, in patients with advanced ovarian cancer has dosed its first patient, Verastem announced.
The study is expected to enroll up to 100 patients at possibly 15 sites across the U.S. It is currently enrolling participants, and information is available on its clinical trials.gov webpage.
“Patients with late-stage ovarian cancer are in dire need of effective new treatments. We are eager to review the results of this important study as we continue to investigate the potential of avelumab to address the unmet needs for this hard-to-treat cancer,” Dr. Alise Reicin, head of Global Clinical Development at Merck KGaA, Darmstadt, Germany’s biopharma business, said in a news release. [Verastem is conducting the study in collaboration with Merck (EMD Serono in the U.S. and Canada) and Pfizer.]
The focal adhesion kinase (FAK) protein, which is found at high levels in several tumors, is thought to aid in tumor immune evasion. Studies have shown that blocking this protein can lower the numbers of immunosuppressive T-cells and increase those of killer T-cells, suggesting that combining a FAK inhibitor with immune checkpoint inhibitors could be a promising approach for cancer patients.
“Our goal, through this collaboration, is to increase our understanding of FAK inhibition, and further demonstrate the alliance’s commitment to exploring a diverse range of novel combinations with avelumab,” said Chris Boshoff, MD, PhD, senior vice president and head of Immuno-oncology, Early Development and Translational Oncology at Pfizer.
The Phase 1/2 trial (NCT02943317) is a multicenter, open-label, two-part study (dose escalation and dose expansion), designed to assess the safety and efficacy of defactinib plus avelumab in patients with recurrent or refractory stage 3 or 4 ovarian cancer.
In the dose escalation part of the study, about 18 patients will receive avelumab in 28 day-cycles (10 mg/kg intravenously on days 1 and 15) and oral defactinib twice daily.
In the absence of a dose-limiting toxicity, each patient will be given a minimum of one cycle, and may continue receiving additional cycles until disease progression or unacceptable toxicity.
After determining optimum dosing for defactinib, the dose expansion part of the trial will begin. This part intends to enroll about 80 patients, receiving avelumab (10 mg/kg on days 1 and 15 of 28-day cycles) plus defactinib at the defined dose.
The study’s primary endpoint is safety and overall response, and secondary endpoints include progression-free survival, overall survival, time to treatment response, and duration of response.
“Initiation of this clinical trial evaluating the combination of avelumab and defactinib represents an important milestone for Verastem, and together with our collaborators at Merck KGaA, Darmstadt, Germany, and Pfizer, we are eager to evaluate the potential of this combination to provide ovarian cancer patients with a new treatment option,” said Robert Forrester, president and chief execcutive officer of Verastem.