BOSTON, Mass. — Verastem Oncology said it will discontinue the RAMP 203 Phase 1/2 clinical trial in advanced KRAS G12C-mutated non-small cell lung cancer following an interim data review, as the company shifts its focus to the clinical development of VS-7375, an oral KRAS G12D (ON/OFF) inhibitor.
The company said there will be no further enrollment in the RAMP 203 study, and patients currently enrolled will have the option to continue treatment at the discretion of investigators. Verastem said the decision reflects changes in the treatment landscape for KRAS G12C inhibitors and its strategic prioritization of programs with the potential for greater patient impact.
“RAMP 203 has provided important insights into treatment strategies and demonstrated proof-of-concept. While avutometinib plus defactinib combined well with a G12C inhibitor to drive early and sustained anti-tumor responses, next generation G12C inhibitors are establishing a new benchmark with higher response rates,” said John Hayslip, chief medical officer at Verastem Oncology. “Accordingly, we are prioritizing our clinical development of VS-7375, a potentially best-in-class oral KRAS G12D (ON/OFF) inhibitor, that demonstrated a 69% response rate (11 of 16, both confirmed and unconfirmed) in advanced KRAS G12D NSCLC and has the potential to help more patients with its differentiated approach in multiple solid tumors; and the RAMP 205 clinical trial evaluating avutometinib plus defactinib in combination with chemotherapy in first line metastatic pancreatic cancer.”
“We sincerely appreciate and thank the investigators, patients, and families who participated in this program as these clinical outcomes will contribute to the development of novel therapies urgently needed for this challenging cancer,” Hayslip added.
RAMP 203 is a Phase 1/2 clinical trial conducted in collaboration with Amgen evaluating avutometinib, an oral RAF/MEK clamp, in combination with LUMAKRAS (sotorasib) as a doublet regimen, and with defactinib, an oral FAK inhibitor, as a triplet regimen. The trial enrolled patients who were either naïve to or previously treated with a KRAS G12C inhibitor.
As of the November 26, 2025 data cutoff, 66 patients treated at the recommended Phase 2 dose had received at least one tumor scan and were evaluable for efficacy. Among KRAS G12C inhibitor-naïve patients receiving the doublet combination, 30 were evaluable and achieved an overall response rate of 40%, with a median progression-free survival of 11.1 months and a median follow-up of 15.9 months. In patients previously treated with a KRAS G12C inhibitor who received the doublet combination, 21 were evaluable, with an overall response rate of 9.5% and a median progression-free survival of 3.7 months, based on a median follow-up of 10.8 months.
In the triplet combination, six KRAS G12C inhibitor-naïve patients were enrolled, with four evaluable for efficacy. This group achieved an overall response rate of 50%, including one confirmed and one unconfirmed response, and one additional patient experienced stable disease. Among patients previously treated with a KRAS G12C inhibitor who received the triplet regimen, 12 were enrolled and 11 were evaluable for efficacy. Four of those patients showed greater than 30% tumor reduction, with seven patients remaining on treatment as of the data cutoff. Median progression-free survival could not be determined for the treatment-naïve triplet cohort, while patients previously treated with a KRAS G12C inhibitor had a median progression-free survival of 3.6 months.
Across both the doublet and triplet regimens, the company said no dose-limiting toxicities were observed. Treatment-related adverse events were generally manageable, with nausea, diarrhea, and fatigue reported as the most common.
Verastem said it is evaluating opportunities to share the RAMP 203 data in the future.
