Verastem Oncology's decision to refocus its R&D efforts on its KRAS inhibitor appears to be paying off, at least based on initial data from a phase 1/2 trial.
The biopharma has been evaluating two doses of VS-7375, its KRAS G12D inhibitor, in the study of over 200 patients with advanced KRAS G12D-mutated solid tumors like metastatic pancreatic ductal adenocarcinoma (mPDAC) and non-small cell lung cancer (NSCLC).
They included 22 evaluable patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received a 900 mg daily dose of VS-7375. This cohort showed a 67% rate of progression-free survival at six months and an 80% overall survival (OS) rate, according to the Oct. 14 release. In total, 16 of these patients remained on treatment by the six-month mark.
Verastem also evaluated the efficacy of VS-7375. Here, half of the eight PDAC patients who received VS-7375 in the second-line setting experienced a response, while 41% of the 22 patients who received the drug in the second-line setting or later saw a response, including two complete responses.
Meanwhile, among the 23 patients with NSCLC who received a 600 mg daily dose of VS-7375, the confirmed ORR was 43% at 4.4 months with a six-month PFS rate of 72%.
VS-7375 is an oral selective KRAS G12D inhibitor designed to engage in both its active (ON) and inactive (OFF) states. KRAS is a gene that gives instructions for a molecular switch that controls cell growth and division. When the KRAS gene is mutated, it can promote cancer development and growth. G12D is a specific genetic mutation that represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers.
The KRAS space was re-energized in August when Revolution Medicines’ RAS inhibitor Rasonque was approved by the FDA for metastatic pancreatic cancer. Rasonque previously showed a 36% confirmed ORR in the second-line setting and 21% in the third-line setting and beyond.
“[VS-7375] and the RAS inhibitors in general are changing the landscape of the way we are managing and treating [PDAC],” Manuel Hidalgo Medina, M.D., Ph.D., director of the gastrointestinal cancer center at New York University (NYU), told investors on a call this morning to discuss the company's data.
Versatem CEO Dan Paterson said on the call that the company had “set a new benchmark in PDAC,” while Chief Scientific Officer Jonathan Pachter, Ph.D., suggested “we have a true blockbuster.”
The results are a welcome validation of Versatem's decision over the summer to channel its R&D efforts into VS-7375 after the company's approved ovarian cancer combo regimen Avmapki and Fakzynja underwhelmed in a PDAC study.
Verastem will now move VS-7375 into a phase 3 trial to evaluate the drug as a monotherapy and in combination with anti-EGFR therapy or chemotherapy. The aim is to launch the study by the end of the year.
“I've spent almost all my career in smaller companies,” Pachter said. “We can be nimble; we can be fast.”
“We can't do things big companies can do, and so this is one where I truly believe partnering makes the pie bigger,” he added. “We are likely to do some kind of partnering in an ideal deal.”