VS-7375 - (TARGET-D 101)

October 14, 2026: Verastem Oncology (NASDAQ: VSTM) reported initial multi-tumor Phase 1/2 TARGET-D 101 data for VS-7375, an oral KRAS G12D inhibitor, and said FDA alignment has been reached on a first-line metastatic PDAC Phase 3 design, with trial opening planned by year-end 2026.

mPDAC: In 22 evaluable 2L+ patients on 900 mg QD monotherapy, confirmed ORR was 41% (9/22), including two complete responses; ORR was 50% in 2L and 36% in 3L/4L. DCR was 86%, 6-month landmark PFS 67%, 6-month OS 80%, and 16/22 remained on treatment. CA19-9 fell by >50% in 15/17 patients with elevated baseline levels; KRAS G12D ctDNA fell ≥50% in 12/12, with 7/12 achieving complete clearance. The planned Phase 3 will compare VS-7375 plus anti-EGFR, VS-7375 plus gemcitabine/nab-paclitaxel, and standard chemotherapy.

mCRC: In 3L+ disease, 900 mg plus anti-EGFR produced 33% ORR (2/6; one confirmed, one unconfirmed); five patients remained on treatment. TARGET-D 203 enrollment is ongoing.

NSCLC: In 2L+ disease, 600 mg monotherapy achieved 43% confirmed ORR (10/23) and 72% 6-month landmark PFS; 17/23 remained on treatment. In 1L combination with chemotherapy/immunotherapy, ORR was 75% (6/8). TARGET-D 202 is evaluating 900 mg.

Safety: At 900 mg monotherapy (n=48), discontinuation due to adverse events was 2%; grade 3 treatment-related adverse events occurred in 10%, with no cumulative toxicity signal. Upcoming milestones include mature mCRC and initial mPDAC combination data by year-end 2026, initial 1L mPDAC GnP data in Q1 2027, and Phase 2 readouts in 2027.