Investors eager for US results on Verastem’s GenFleet-partnered KRAS G12D inhibitor VS-7375 will have to wait a little longer for a substantial data drop. Although the company is due to give an update from its global phase 1/2 solid tumour trial this half, this will focus on pharmacokinetic and safety data, with perhaps some cases studies, execs have told ApexOnco.
In the second half, however, Verastem will release a more fulsome dataset. And by then it should have several phase 2 trials under way that, if all goes to plan, could support accelerated approval filings next year.
The new studies will be in relapsed pancreatic ductal adenocarcinoma, non-small cell lung cancer and colorectal cancer – although they will also include first-line cohorts. They will primarily evaluate overall response rates, said Verastem’s chief scientific officer, Jonathan Pachter.
Separate phase 2
That's a departure for Verastem, which had originally hoped that accelerated filings could be supported by upsized cohorts from its phase 1/2 study, now known as Target-D 101.
However, “the FDA responded that, if you’re pursuing market authorisation, you really ought to set up separate phase 2s”, Pachter said. Although the mid-stage trials aren’t currently listed on clinicaltrials.gov, they should be “soon”.
The company is also planning randomised phase 3 trials in first-line disease, intended to confirm and expand any accelerated nods. These could start as early as late 2026, but the timing will depend on “how things progress”. Ultimately, these studies will need to be substantially under way for Verastem to file for accelerated approval, which it hopes to do by mid-2027.
Verastem’s planned phase 2 studies of VS-7375
| Trial | Details | Note |
|---|
| Target-D 201 | PDAC: 2nd-line PDAC (+/- Erbitux); 1st-line (+ Erbitux) | To start mid-2026; could support AA filings mid-2027 |
| Target-D 202 | 2nd/3rd-line NSCLC |
| Target-D 203 | CRC: 2nd-line (+/- Erbitux or Vectibix); 1st-line (+ chemo) |
The company formally licensed VS-7375 from GenFleet in January 2025 for an undisclosed fee, but the groups have been working together since 2023 on RAS-targeting projects.
Verastem believes that VS-7375, also known as GFH375, could have advantages over other KRAS inhibitors by virtue of hitting both the “on” and “off” states; projects from Revolution Medicines, for example, only inhibit the “on”, or GTP-bound (active) form of RAS.
However, efficacy data on VS-7375 have so far only come from a Chinese phase 1/2 trial. At last year’s ESMO meeting GenFleet claimed a 41% ORR among 59 relapsed PDAC patients receiving a 600mg dose, but this number included unconfirmed responses. It also represented a waning from the 52% ORR reported at ASCO 2025.
So far, Verastem hasn’t revealed much from Target-D 101. In its fourth-quarter earnings release in March the company said it had cleared a 900mg daily monotherapy dose with no dose-limiting toxicities, and escalation has continued to 1.2g daily. The company is also testing a 900mg daily dose in combination with Erbitux.
Verastem also described VS-7375 as “generally well tolerated”, with no drug-related liver function test abnormalities, and no drug-related neutropenia greater than grade 2.
Although GenFleet is taking the 600mg dose forward, Pachter reckons that 900mg “will be the dose we arrive at”.
The second-half release should encompass efficacy from “double-digit” numbers of patients in PDAC, NSCLC and colorectal cancer at the recommended phase 2 dose. US data in a substantial population will be needed to lift interest in Verastem, whose $500m market cap is dwarfed by some of the other KRAS players, such as Revolution and Erasca.
