Key Takeaways
- • Verastem Oncology reported initial phase 1/2 data for VS-7375, its oral selective KRAS G12D inhibitor, in a study of over 200 patients with advanced KRAS G12D-mutated solid tumors, with results released October 14.
- • In 22 evaluable metastatic pancreatic ductal adenocarcinoma (mPDAC) patients receiving 900 mg daily, the cohort showed a 67% six-month progression-free survival rate and an 80% overall survival rate, according to the company release.
- • Among 23 non-small cell lung cancer (NSCLC) patients receiving 600 mg daily, the confirmed objective response rate was 43% at 4.4 months, with a six-month PFS rate of 72%.
- • Verastem will advance VS-7375 into a phase 3 trial as a monotherapy and in combination with anti-EGFR therapy or chemotherapy, with a launch targeted by year-end.
- • CEO Dan Paterson said the company has "set a new benchmark in PDAC," while CSO Jonathan Pachter said "we have a true blockbuster" and signaled likely partnering.
Summary
Verastem Oncology's decision to refocus its research and development efforts on its KRAS inhibitor appears to be yielding early results, according to initial data from a phase 1/2 trial of VS-7375. The study evaluated two doses of the drug in more than 200 patients with advanced KRAS G12D-mutated solid tumors, including metastatic pancreatic ductal adenocarcinoma (mPDAC) and non-small cell lung cancer (NSCLC). VS-7375 is an oral selective KRAS G12D inhibitor designed to engage both the active (ON) and inactive (OFF) states of the KRAS protein. G12D represents 26% of all KRAS mutations and is the most prevalent KRAS mutation in human cancers.
In the pancreatic cohort, 22 evaluable patients receiving 900 mg daily showed a 67% progression-free survival rate at six months and an 80% overall survival rate, per the October 14 release. Sixteen of these patients remained on treatment at the six-month mark. Among eight PDAC patients who received VS-7375 in the second-line setting, half experienced a response. Across 22 patients receiving the drug in the second-line setting or later, 41% saw a response, including two complete responses. In the NSCLC cohort, 23 patients receiving 600 mg daily had a confirmed objective response rate of 43% at 4.4 months and a six-month PFS rate of 72%.
The data arrive after Revolution Medicines' RAS inhibitor was approved by the FDA in August for metastatic pancreatic cancer, a development that re-energized the KRAS space. That drug previously showed a 36% confirmed ORR in the second-line setting and 21% in the third-line setting and beyond. Manuel Hidalgo Medina, M.D., Ph.D., director of the gastrointestinal cancer center at New York University, told investors that VS-7375 and RAS inhibitors in general are changing how PDAC is managed and treated.
The results also validate Verastem's summer decision to channel R&D resources into VS-7375 after its approved ovarian cancer combination, Avmapki Fakzynja, underwhelmed in a PDAC study. Verastem plans to launch a phase 3 trial by year-end to evaluate VS-7375 as a monotherapy and in combination with anti-EGFR therapy or chemotherapy. Chief Scientific Officer Jonathan Pachter said the company is nimble and fast-moving, and that it is likely to pursue partnering: "We are likely to do some kind of partnering in an ideal deal."
In the pancreatic cohort, 22 evaluable patients receiving 900 mg daily showed a 67% progression-free survival rate at six months and an 80% overall survival rate, per the October 14 release. Sixteen of these patients remained on treatment at the six-month mark. Among eight PDAC patients who received VS-7375 in the second-line setting, half experienced a response. Across 22 patients receiving the drug in the second-line setting or later, 41% saw a response, including two complete responses. In the NSCLC cohort, 23 patients receiving 600 mg daily had a confirmed objective response rate of 43% at 4.4 months and a six-month PFS rate of 72%.
The data arrive after Revolution Medicines' RAS inhibitor was approved by the FDA in August for metastatic pancreatic cancer, a development that re-energized the KRAS space. That drug previously showed a 36% confirmed ORR in the second-line setting and 21% in the third-line setting and beyond. Manuel Hidalgo Medina, M.D., Ph.D., director of the gastrointestinal cancer center at New York University, told investors that VS-7375 and RAS inhibitors in general are changing how PDAC is managed and treated.
The results also validate Verastem's summer decision to channel R&D resources into VS-7375 after its approved ovarian cancer combination, Avmapki Fakzynja, underwhelmed in a PDAC study. Verastem plans to launch a phase 3 trial by year-end to evaluate VS-7375 as a monotherapy and in combination with anti-EGFR therapy or chemotherapy. Chief Scientific Officer Jonathan Pachter said the company is nimble and fast-moving, and that it is likely to pursue partnering: "We are likely to do some kind of partnering in an ideal deal."
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