Verastem Oncology (Nasdaq: VSTM) released initial efficacy and updated safety data from its ongoing TARGET-D 101 Phase 1/2 clinical trial evaluating VS-7375, an investigational oral KRAS G12D inhibitor, in patients with advanced KRAS G12D-mutated solid tumors, according to a company statement.

In metastatic pancreatic ductal adenocarcinoma (mPDAC), 22 patients treated with VS-7375 at 900 mg once daily showed a 50% confirmed objective response rate (ORR) in the second-line setting, a 41% confirmed ORR across the second-line and later population, and a 36% confirmed ORR in the third- and fourth-line setting. Two complete responses were observed. The disease control rate was 86%, the six-month landmark progression-free survival rate was 67%, and the six-month overall survival rate was 80%. A majority of patients, 16 of 22, remained on treatment at the time of the data cutoff.

In advanced non-small cell lung cancer, 23 patients treated with 600 mg once daily showed a 43% confirmed ORR in the second-line and later setting, with a six-month landmark progression-free survival rate of 72%. In metastatic colorectal cancer, six patients treated with 900 mg in combination with anti-EGFR therapy showed a 33% unconfirmed ORR in the third-line and later setting.

The company reported a 2% discontinuation rate due to adverse events at the 900 mg monotherapy dose across 48 patients. Treatment-related adverse events were primarily low-grade gastrointestinal effects. No cumulative toxicities were observed with longer follow-up.

Verastem said it has reached alignment with the U.S. Food and Drug Administration on a Phase 3 trial design evaluating VS-7375 in the first-line mPDAC setting. The three-arm study will compare a chemotherapy-free regimen of VS-7375 with anti-EGFR, VS-7375 combined with gemcitabine/nab-paclitaxel, and investigator-choice standard-of-care chemotherapy. The company plans to open the trial by year-end 2026.

Verastem also plans to meet with the FDA before year-end to discuss Phase 3 trial designs in first-line metastatic colorectal cancer and first-line advanced non-small cell lung cancer, with first patient enrollment in those trials targeted for the first half of 2027.