Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types, including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma.

Product Profile

Defactinib is an oral small molecule inhibitor of FAK and PYK2. Verastem Oncology™ has patent protection for defactinib through 2029, and has received orphan drug designation for defactinib in ovarian and mesothelioma in the US, the EU, and Australia.

Clinical Development in Advanced Cancers

Defactinib has been studied in over 300 patients and has shown a well-tolerated safety profile. Initial signs of activity has been observed in clinical studies as a monotherapy in KRAS mt (mutation) NSCLC and in relapsed ovarian cancer in combination with paclitaxel have been observed.

Clinical Investigation of Defactinib Combinations

Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the central role FAK signaling has in effectively reducing cancer stem cells, enhancing immune response by decreasing immuno-suppressive cells and increasing cytotoxic T cells and reducing stromal density, which allows both drug and tumor-killing immune cells to enter the tumor. Additionally, immuno-modulatory effects were shown to substantially increase survival of mice when FAK inhibitors were combined with an anti-PD-1 immune checkpoint antibody. These results have indicated the potential promise of combination therapy in future clinical studies.

Defactinib is currently being evaluated as a potential combination therapy for pancreatic cancer, NSCLC, ovarian cancer and mesothelioma.

Ongoing studies with defactinib include:

A Phase 1b study in combination with Merck & Co.’s PD-1 inhibitor pembrolizumab and gemcitabine in patients with advanced pancreatic cancer. To learn more about this study, visit

A Phase 1/2 collaboration with Pfizer Inc. and Merck KGaA to evaluate combination therapy with avelumab, an anti-PD-L1 antibody, in patients with relapsed ovarian cancer. To learn more about this study, visit

A Phase 1/2 collaboration with Merck & Co. and Cancer Research UK to evaluate combination therapy with pembrolizumab. Following dose escalation, three expansion arms are planned in NSCLC, relapsed pancreatic cancer and mesothelioma. To learn more about these studies, visit (NSCLC study | mesothelioma study).