Verastem Oncology Shuts Down KRAS G12C RAMP-203 Trial, 69% Response in KRAS G12D Study
Verastem Oncology has discontinued its RAMP-203 Phase 1/2 trial for advanced KRAS G12C NSCLC to reallocate resources to VS-7375, an oral KRAS G12D inhibitor. VS-7375 demonstrated a 69% response rate (11/16) in KRAS G12D NSCLC patients, with interim Phase 1/2a data expected in 1H 2026.
1. Analyst Downgrades Verastem to Buy After RAMP-203 Discontinuation
Following an interim review of the RAMP-203 Phase 1/2 trial in advanced KRAS G12C NSCLC, Verastem Oncology (Nasdaq: VSTM) has been downgraded by a leading biotech equity research team from Strong Buy to Buy. The decision reflects the company’s choice to halt enrollment in RAMP-203 — which evaluated avutometinib plus defactinib in doublet and triplet combinations with Amgen’s KRAS G12C inhibitor — and reallocate resources to programs with higher near-term potential. Investors are weighing the impact of this pivot on Verastem’s near-term clinical milestones and cash runway, given the company ended Q3 2025 with approximately $180 million in cash and equivalents.
2. RAMP-203 Provided Proof-of-Concept but Lagged Next-Gen Inhibitors
As of the November 26, 2025 cutoff, 66 patients treated at the recommended Phase 2 dose had at least one tumor scan. In treatment-naïve patients on the doublet regimen, the overall response rate was 40% (12 of 30) with a median progression-free survival of 11.1 months (median follow-up: 15.9 months). Among previously treated patients, ORR was 9.5% (2 of 21) and mPFS 3.7 months (follow-up: 10.8 months). The triplet arm showed a 50% ORR (2 of 4) in treatment-naïve patients and 36% tumor reduction in 4 of 11 previously treated patients. No dose-limiting toxicities were observed, and safety was manageable, with nausea (56.8%), diarrhea (52.7%) and fatigue (45.9%) most common. However, next-generation G12C inhibitors have since set higher benchmarks, prompting Verastem’s strategic shift.
3. VS-7375 in KRAS G12D Poised as Key Catalyst in 1H 2026
Verastem is now concentrating on VS-7375, its oral KRAS G12D ON/OFF inhibitor, which delivered a 69% response rate (11 of 16 patients, confirmed and unconfirmed) in early NSCLC cohorts. The company plans to present interim Phase 1/2a U.S. data in 1H 2026 for VS-7375 across KRAS G12D solid tumors, a readout that could validate its differentiated mechanism and drive a re-rating of the stock. Management has highlighted the broader addressable market in KRAS G12D malignancies — potentially double the size of G12C — and expects to initiate combination studies in second half 2026 pending regulatory feedback.