Verastem's VS-7375 hits 50% response in second-line pancreatic cancer, Phase 3 next

What happened

Verastem reported its first multi-tumor efficacy and safety update for VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor, in an 8-K filed on 14 October 2026 ^[1]. In the TARGET-D 101 Phase 1/2 trial, 900 mg once-daily monotherapy produced a 50% confirmed response rate (4 of 8) in second-line pancreatic cancer, 41% (9 of 22) across the broader second-line-plus group including two complete responses (one confirmed), and 36% (5 of 14) in the third- and fourth-line setting, as of a 7 October 2026 data cutoff ^[1]. Disease control reached 86% in the second-line-plus group, with a six-month landmark progression-free survival rate of 67% and a six-month overall survival rate of 80% ^[1]. The discontinuation rate from adverse events at that dose was 2% ^[1]. VS-7375 also showed a 43% confirmed response rate at 600 mg daily in second-line-plus non-small cell lung cancer and a 33% unconfirmed response with 900 mg plus anti-EGFR therapy in heavily pretreated third-line-plus colorectal cancer ^[1].

Why it matters

Pancreatic ductal adenocarcinoma is where the next-wave KRAS agents are competing, per Endpoints News, which framed the day as Verastem staking its claim as a competitor to Revolution Medicines ^[3]. Revolution Medicines' RAS(ON) candidate daraxonrasib entered this disease through an FDA "safe to proceed" letter authorizing an expanded access protocol ^[8]. That event sets the contrast: Verastem is reporting confirmed single-agent activity in pretreated patients, while the FDA letter for daraxonrasib authorizes treatment use outside a trial, not an efficacy readout ^[8]. Monotherapy response at this level is uncommon in a disease where pretreated response rates are typically low.

The context behind the number

Verastem already sells avutometinib plus defactinib as AVMAPKI FAKZYNJA CO-PACK, the first FDA-approved treatment for KRAS-mutated recurrent low-grade serous ovarian cancer, and that combination generated $25.1 million in net product revenue in the second quarter of 2026 ^[2][7]. In pancreatic cancer, the same combination with gemcitabine and nab-paclitaxel delivered a 52% confirmed response rate, 68% six-month PFS and 86% six-month OS in the 29-patient RAMP 205 cohort reported on 17 June 2026 ^[6]. VS-7375 is the newer, oral bet, and it is the asset Verastem is moving toward a registrational trial.

What to watch next

Verastem said it has aligned with the FDA on a Phase 3 design in first-line metastatic pancreatic cancer and plans to open that trial by year-end 2026 ^[1]. Two registered combination studies bracket the timeline: the Verastem-sponsored trial of the combo with gemcitabine and nab-paclitaxel (NCT05669482) is active but no longer recruiting, with a primary completion date of 31 August 2026 ^[4]; a University of Virginia neoadjuvant study pairing the combo with mFOLFIRINOX (NCT07824960) is not yet open ^[5]. On the corporate side, Michael P.

The now-what

For RAS-targeting developers, VS-7375's second-line monotherapy numbers reset the single-agent benchmark; teams holding combination data should re-baseline against it before Verastem's first-line Phase 3 locks a comparator. BD groups weighing RAS assets face a narrowing window as the program moves from Phase 1/2 signal to a design-aligned Phase 3 within months.

What Prognyx could not verify

The TARGET-D 101 registry entry, including its trial identifier and current status, is not in the public set Prognyx reviewed; the response figures come from Verastem's own filing ^[1]. The $250 million raise appears in the Endpoints News report ^[3]; Prognyx could not confirm its size, structure or investors from a Verastem financing filing.

Verdict