On April 2, 2017 Verastem, Inc. (NASDAQ: VSTM), focused on discovering and developing drugs to treat cancer, reported the oral presentation of data for its lead focal adhesion kinase (FAK) inhibitor, defactinib, by the Company’s scientific collaborator David G. DeNardo, PhD, Assistant Professor of Medicine, Division of Oncology, Department of Immunology, Washington University School of Medicine in St. Louis, at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Washington, DC (Press release, Verastem, APR 2, 2017, View Source [SID1234518406]). Schedule your 30 min Free 1stOncology Demo! In an oral presentation titled, "Reprogramming the tumor microenvironment to improve responses to therapy," Dr. DeNardo described data demonstrating that FAK inhibition can enable efficacy of PD-1 inhibition in preclinical models of pancreatic cancer that, like the clinical disease, are otherwise refractory to checkpoint inhibition. As described in Dr. DeNardo’s presentation, a clinical trial is in progress, which combines Verastem’s FAK inhibitor defactinib with Merck’s PD-1 inhibitor pembrolizumab together with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Initial analysis of immune biomarkers from matched pairs of metastatic biopsies, taken either pre or post treatment, from patients with PDAC has been conducted in this study.
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"Immunotherapeutic agents have shown little clinical benefit in pancreatic cancer and this is likely due, at least in part, to the presence of an immunosuppressive tumor microenvironment including a dense stroma which may prevent T cell entry into, or function within, tumor tissues," said Dr. DeNardo. "Our initial biomarker data, indicating an increase in activated proliferating cytotoxic T cells together with a reduction in tumor-associated macrophages (TAMs) appear promising. We are extremely interested to see whether these immune changes that may shift the balance from immunosuppressive to immunoreactive tumors, may translate into a clinical benefit for pancreatic cancer patients who have few effective treatment options."
Jonathan Pachter, PhD, Verastem’s Chief Scientific Officer, added, "Pancreatic cancer has the highest mortality rate of all major cancers, and the disease is still considered largely incurable. The data presented today by Dr. DeNardo at AACR (Free AACR Whitepaper) 2017 provide important support and rationale for the ongoing clinical study evaluating Verastem’s lead FAK inhibitor defactinib in combination with pembrolizumab and gemcitabine in patients with pancreatic cancer."
The ongoing Phase 1 clinical trial is being conducted at the Washington University School of Medicine in St. Louis under the direction of Andrea Wang-Gillam, MD, PhD, Clinical Director of the Gastrointestinal Oncology Program with financial support from the Precision Medicine Research Associates and the BJH Foundation. The trial, which is expected to enroll approximately 50 patients, is currently completing its dose-escalation portion.
Details for the oral symposium presentation at AACR (Free AACR Whitepaper) 2017 are:
Title: Reprogramming the Tumor Microenvironment to Facilitate Responses to Immunotherapy
Session: Major Symposium; SY14 – Myelomonocytic Cells and Stroma as Therapeutic Targets
Location: Room 206 – Level 2 Washington Convention Center
Date and time: Sunday, April 2, 2017 from 2:05-2:30pm ET
A copy of the oral presentation slides will be available here following the conclusion of Dr. DeNardo’s presentation and a webcast will be available from AACR (Free AACR Whitepaper) beginning on April 26, 2017.
About the Tumor Microenvironment
The tumor microenvironment encompasses multiple tumor and non-tumor cell populations and an extracellular matrix that support cancer cell survival. This includes immunosuppressive regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, cancer-associated fibroblasts and extracellular matrix proteins that can hamper the entry and therapeutic benefit of cytotoxic T cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s product candidates, including duvelisib and defactinib, also target the tumor microenvironment to potentially improve a patient’s response to therapy.
About Defactinib
Defactinib is an investigational inhibitor of FAK, a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signaling in response to cellular adhesion and growth factors.1 Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumor microenvironment, enhancement of anti-tumor immunity, and reduction of cancer stem cells.2,3 Defactinib is currently being evaluated in combination with immunotherapy for the treatment of pancreatic cancer, ovarian cancer, non-small cell lung cancer, and mesothelioma, in three combination clinical trials with pembrolizumab or avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.4,5,6 Information about these and additional clinical trials evaluating the safety and efficacy of defactinib can be found on www.clinicaltrials.gov.