VS-7375 - (TARGET-D 101)

June 23, 2026: Verastem Oncology (NASDAQ: VSTM) reported positive preliminary data from the ongoing TARGET-D 101 Phase 1/2 trial of VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, in advanced KRAS G12D-mutated solid tumors (mPDAC, mCRC, advanced NSCLC). Dose escalation is ongoing up to 1200 mg QD; 900 mg QD achieves target plasma levels with separation vs 600 mg.

Efficacy highlights (early): In previously treated mPDAC, 93% (13/14) of heavily pretreated patients on 900 mg QD monotherapy had >50% CA19-9 reduction; all remain on treatment. Cetuximab combination showed deeper/faster tumor reductions, including at 400 mg QD. VS-7375 600 mg QD + full-dose gemcitabine/nab-paclitaxel was DLT-cleared; enrollment ongoing for 900 mg + full-dose Gem/NabP. In mCRC, VS-7375 + full-dose cetuximab showed promising activity at 600/900 mg; 900 mg + cetuximab was DLT-cleared in May 2026, with additional enrollment planned in TARGET-D 203. In NSCLC, promising activity was seen with 600 mg monotherapy; 900 mg will be studied in TARGET-D 202.

Safety (June 12, 2026 cutoff): manageable GI TRAEs (mostly low-grade) attenuating after cycle 1; one grade 3 nausea at 900 mg; low rash; no meaningful cytopenias or LFT abnormalities.

Business/collaboration: Verastem and Erasca intend to evaluate VS-7375 with ERAS-0015 (pan-RAS molecular glue) preclinically, with potential future clinical collaboration.

Upcoming milestones: TARGET-D 101 update in 2H 2026; complete key TARGET-D 101 cohort enrollments by end of June 2026; announce first patient dosed in TARGET-D 202/203 in mid-2026; complete Phase 2 enrollments by end of 2026; FDA meeting before end of 2026 for Phase 3 designs; first patient in Phase 3 trials in 1H 2027. First patient was dosed in TARGET-D 201 on June 16, 2026. A conference call/webcast is scheduled June 23 at 4:30 p.m. ET.