Sometimes in drug development, you have to know when to fold. Verastem Oncology (VSTM) announced Monday that it's discontinuing the RAMP 203 trial in advanced KRAS G12C-mutated non-small cell lung cancer after taking a hard look at interim data and the competitive landscape. The short version? The field got crowded fast, and next-generation KRAS G12C inhibitors are setting response benchmarks that make the original plan less attractive.
Enrollment in RAMP 203 is stopping immediately, though patients already in the trial can continue treatment if their doctors think it makes sense. This isn't necessarily a reflection on the drug itself, it's more about strategic allocation of finite resources in an increasingly competitive market.
Here's what's happening with those resources: Verastem is doubling down on VS-7375, an oral KRAS G12D (ON/OFF) inhibitor that's showing more promise in advanced non-small cell lung cancer and other solid tumors. According to an SEC filing, management sees stronger strategic potential here, and the early numbers back that up. VS-7375 has achieved a 69% response rate in advanced KRAS G12D lung cancer, with 11 of 16 patients responding (confirmed and unconfirmed). That's the kind of signal that gets attention.
The company is also continuing RAMP 205, which is evaluating avutometinib plus defactinib with chemotherapy in first-line metastatic pancreatic cancer. So this isn't about retreating from cancer research, it's about picking the battles where you have the best shot at winning.
For context, RAMP 203 was a Phase 1/2 study conducted with Amgen Inc. (AMGN) that evaluated avutometinib with Lumakras (sotorasib) as a doublet combination, and with defactinib as a triplet, in patients with KRAS G12C-mutated lung cancer. The trial had potential, but the competitive environment shifted dramatically.
The Competition That Changed the Game
Let's talk about why Verastem is pivoting. The KRAS G12C space has become intensely competitive, with heavyweight pharma companies bringing next-generation inhibitors that are raising the bar significantly.
In May 2025, Merck & Co. Inc. (MRK) shared safety and efficacy results from the Phase 1 KANDLELIT-001 study of MK-1084, a KRAS G12C covalent inhibitor. The drug showed a manageable safety profile and antitumor activity in patients with advanced KRAS G12C-mutated colorectal cancer and lung cancer, both as monotherapy and in combinations with other therapies. That's a formidable competitor right there.
Then in September 2025, the FDA granted Breakthrough Therapy designation to Eli Lilly and Co.'s (LLY) olomorasib in combination with Merck's Keytruda (pembrolizumab) for first-line treatment of unresectable advanced or metastatic lung cancer with a KRAS G12C mutation and PD-L1 expression of 50% or higher. Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C with preliminary evidence of central nervous system activity, which is particularly valuable since brain metastases are a major concern in lung cancer.
When you're a smaller biotech competing against drugs from Merck and Lilly that are getting breakthrough designations and showing strong clinical activity, you have to think carefully about where to deploy your capital and talent. Verastem appears to have made the calculation that VS-7375, targeting KRAS G12D rather than G12C, offers a better risk-reward profile given the current landscape.
Shares of Verastem were down 4.34% at $7.75 at the time of publication on Friday, according to market data. That's a modest reaction, suggesting investors may understand the strategic rationale for the pivot rather than viewing it as a failure.




