FAK Inhibitor Boosts Anti-PD1 Immunotherapy in Pancreatic Cancer

At the American Society of Clinical Oncology (ASCO) annual meeting, researchers reported the results of pembrolizumab (Keytruda), a PD-1 immune checkpoint inhibitor, with or without defactinib, a novel focal adhesion kinase (FAK) inhibitor, as sequential neoadjuvant and adjuvant therapy in patients with high-risk resectable pancreatic ductal adenocarcinoma.

In this exclusive MedPage Today video, Jun Gong, MD, from the Samuel Oschin Cancer Center at Cedars-Sinai in Los Angeles, discusses the phase II trial and the expanding horizon of other immune therapy studies.

Following is a transcript of his remarks:

This is the study specifically led by my partner and friend and colleague, Dr. Arsen Osipov, which is funded by the NIH “K” mechanism, as well as the ASCO Conquer Cancer Foundation.

This is a pancreatic cancer study. It’s a randomized phase II study investigating the efficacy of an immune therapy combination with a focal adhesion kinase, or FAK, inhibitor, as part of a neoadjuvant approach to resectable pancreatic cancer.

Overall, some background about the study: pancreatic cancer remains a very lethal disease where breakthroughs in therapy and in management are a high unmet need. So in this space, we targeted a localized pancreatic cancer population — those who are candidates for surgical resection, who must have had stage IIA or less disease by stage, and they must have been deemed high risk with a CA19-9 greater than 200.

And in this study, patients were enrolled to one of two arms. In the first arm, patients did receive neoadjuvant chemotherapy, also known as preoperative chemotherapy, of gemcitabine [Gemzar]-Abraxane [nab-paclitaxel] for two cycles. Then they underwent a biopsy, then they were enrolled to receive the PD-1 inhibitor pembrolizumab plus the focal adhesion kinase inhibitor defactinib. This was then followed by surgical resection.

In the other arm, patients again received gemcitabine-Abraxane, two cycles, followed by biopsies, and then they were randomized to receive pembrolizumab alone, followed by surgical resection.

Dr. Osipov and his team evaluated with multiplex immunohistochemistry, using pre-immunotherapy and post-immunotherapy specimens. What they saw is that the group that received immune therapy plus the FAK inhibitor, they saw a decrease in fibroblast infiltration. They saw an increase in M1 antitumor macrophage expression. They also saw an increase in CD8-positive tumor-infiltrating lymphocytes.

What does this mean? These are all markers of immune populations that have correlated with outcomes and improved efficacy. Actually decreasing fibroblasts is an immunosuppressive population, so you want those lower. But you want higher populations of the active anti-tumor immune cells — in this case, the M1 and the CD8 T-cells.

So I think what Dr. Osipov’s team shows in this breakthrough study is that treatment with this immune therapy combination is actually successfully able to regulate the tumor microenvironment around the tumor, increasing the population of good immune cells that would treat the cancer, and lowering those that may be bad or prohibitive against your anti-cancer activity. So we’re hoping that this study will lead to further advancements in this phase of pancreatic cancer therapy and improve outcomes for everybody.

As Dr. Osipov will tell you, there are growing numbers of other studies of immune therapies in general. This was a collaboration with the Hopkins Cancer Center and their pioneers with cancer vaccines, which they’re pioneering with pancreatic cancer and other tumor types. And then there are other groups around the country that are doing more novel immunotherapy approaches — CAR [chimeric antigen receptor] T-cell therapy is another immunotherapy approach; bispecific antibodies with immunotherapies are also expanding on the horizon.

So I think the future is very bright with immunotherapy-based combinations in pancreatic cancer and other solid tumors in general.

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