Shares of Verastem Inc (NASDAQ:VSTM) declined roughly 5% in after-hours trading Tuesday after the company released preliminary clinical data for VS-7375, its investigational oral KRAS G12D inhibitor.
Verastem disclosed early results from the ongoing TARGET-D 101 Phase 1/2 trial, reporting anti-tumor activity observed across multiple dose levels in patients with advanced solid tumors harboring the KRAS G12D mutation. Tumor types included in the dataset were metastatic pancreatic ductal adenocarcinoma, metastatic colorectal cancer, and advanced non-small cell lung cancer.
In the metastatic pancreatic cancer cohort, the company reported that 93% of heavily pretreated patients receiving 900 mg once daily monotherapy achieved reductions greater than 50% in the tumor marker CA19-9. The company noted that all 14 evaluable patients in that cohort remained on treatment at the time of the data cutoff.
Safety observations from the trial were characterized primarily by low-grade gastrointestinal adverse events - specifically nausea, vomiting, and diarrhea - with the company reporting these events generally decreased after the first treatment cycle. There was one Grade 3 instance of nausea at the 900 mg dose level; that event resolved within four days, according to the data released.
Verastem said dose escalation is continuing at 1,200 mg once daily. Separately, the company has initiated three Phase 2 registration-directed studies and intends to complete enrollment across those trials by the end of 2026.
The company also announced an intent to collaborate with Erasca Inc to evaluate VS-7375 in combination with ERAS-0015, described as Erasca’s investigational pan-RAS molecular glue, in patients with advanced KRAS G12D-mutant solid tumors.
Verastem plans to meet with the U.S. Food and Drug Administration before year-end to review Phase 3 pivotal trial designs in first-line metastatic pancreatic cancer, first-line metastatic colorectal cancer, and first-line advanced non-small cell lung cancer. The company said enrollment in Phase 3 trials is expected to begin in the first half of 2027.
Context and implications
The update combines early efficacy signals - including CA19-9 reductions in the pancreatic cohort - with a safety profile dominated by low-grade gastrointestinal effects that reportedly subsided after the initial cycle. Dose escalation and combination assessments with Erasca are ongoing, and the company has outlined a path toward registration-directed Phase 2 studies and future Phase 3 discussions with regulators.
This release of preliminary data was followed by a roughly 5% drop in Verastem shares in after-hours trading on the same day.