Verastem (VSTM) Study update summary

Study overview

• TARGET-D 101 Phase 1/2 enrolled >200 patients with advanced KRAS G12D-mutated solid tumors; 900 mg QD advanced across tumor types, with 1,200 mg QD evaluation ongoing. Efficacy cutoff was Oct. 7, 2026; safety cutoff was Sept. 29, 2026.

• VS-7375 is a selective KRAS G12D inhibitor designed for potent, balanced ON/OFF inhibition; 900 mg exposures reached or exceeded preclinical targets associated with maximal antitumor efficacy.

Pancreatic cancer

• At 900 mg QD monotherapy in mPDAC, confirmed ORR was 41% (9/22): 50% (4/8) in 2L and 36% (5/14) in 3L/4L; responses included two complete responses, one confirmed and one unconfirmed.

• In 2L+ PDAC, DCR was 86%, 6-month landmark PFS was 67%, 6-month landmark OS was 80%, and median follow-up was 6.4 months; 16/22 remained on treatment and 15/22 had no progression.

• Among 12 evaluable patients with detectable baseline ctDNA, all had ≥50% VAF reductions, 11/12 had ≥90% reductions, and 7/12 cleared detectable ctDNA by cycle 3 day 1; 15/17 with elevated baseline CA19-9 had >50% reductions.

• A 900 mg monotherapy patient had a confirmed partial response at week 12, with a 47% target-lesion reduction and ongoing response; investigator-reported pain resolved within one week.

Colorectal and lung cancer

• In 3L+ mCRC, 900 mg QD plus anti-EGFR therapy produced a 33% ORR (2/6; one confirmed and one unconfirmed); five patients remained on treatment.

• Early colorectal data at 900 mg showed tumor shrinkage in all five patients with scan data; one response was confirmed and another unconfirmed, with six patients in the MITT denominator.

• In 2L+ NSCLC, 600 mg QD monotherapy achieved a 43% confirmed ORR (10/23); 6-month landmark PFS was 72%, median PFS was not reached, and 17/23 remained on treatment.

• In 1L KRAS G12D lung adenocarcinoma, 600 mg QD with platinum-pemetrexed-based regimens, with or without pembrolizumab, showed a 75% ORR (6/8); six patients remained on treatment.