Verastem Oncology announced the discontinuation of its RAMP‑203 Phase 1/2 study of the combination of avutometinib and defactinib in patients with advanced KRAS G12C‑mutated non‑small cell lung cancer. The decision followed an interim data review that showed the doublet and triplet regimens had limited benefit compared with newer KRAS G12C inhibitors and a narrow therapeutic window.
The data cutoff for the study was November 26, 2025. In treatment‑naïve patients, the doublet regimen produced an overall response rate (ORR) of 40 % (12 of 30) and a median progression‑free survival (mPFS) of 11.1 months. In patients previously treated with a KRAS G12C inhibitor, the doublet yielded an ORR of 9.5 % (2 of 21) and an mPFS of 3.7 months. The triplet regimen achieved an ORR of 50 % (2 of 4) in treatment‑naïve patients and a 36 % reduction in tumor size in 4 of 11 previously treated patients.
Verastem’s strategic pivot centers on VS‑7375, an oral KRAS G12D inhibitor developed in partnership with GenFleet Therapeutics. VS‑7375 has earned Fast Track designation from the FDA for KRAS G12D‑mutated pancreatic cancer and has shown a 69 % response rate in a Phase 1/2 study of advanced KRAS G12D NSCLC, underscoring its higher clinical and commercial potential relative to the discontinued program.
The company’s financial profile highlights a rapid cash burn and a negative EBITDA of approximately $160 million over the past year, with a market capitalization near $595 million. The discontinuation of RAMP‑203 and the reallocation of resources to VS‑7375 are intended to improve the pipeline’s overall value proposition and to address the company’s liquidity constraints.
Chief Medical Officer John Hayslip said the RAMP‑203 data provided “important insights” and confirmed that next‑generation KRAS G12C inhibitors are setting new benchmarks. He added that the decision to focus on VS‑7375 reflects the company’s confidence in the 69 % response rate observed in early trials and the broader therapeutic opportunity in KRAS G12D‑mutated cancers.
Investors reacted negatively to the announcement, with the market responding to the halt of a key program and the shift toward a still‑early‑stage candidate. The decision also signals a broader realignment of Verastem’s pipeline priorities, as the company continues the RAMP‑205 study of the same combination in first‑line metastatic pancreatic cancer.
The RAMP‑205 trial remains active, and Verastem plans to continue investing in its KRAS‑targeted portfolio while reallocating resources to accelerate VS‑7375 development. The company’s leadership views the pivot as a necessary step to focus on the most promising therapeutic opportunities and to manage its financial position more effectively.
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