Pfizer trims its pan-KRAS efforts

19 January 2026

The “next-gen” PF-07985045 is gone, but the group has another pan-KRAS shot.

Pfizer is continuing its new-year clearout, ditching two more projects: the pan-KRAS inhibitor PF-07985045 and the PD-L1-targeting conjugate PF-08046037. The demise of the latter, which uses a TLR7 agonist payload, is perhaps not surprising given that Pfizer recently jumped into phase 3 with a more conventional PD-L1 ADC, fetrastobart vedotin.

Meanwhile, the pan-KRAS exit might initially suggest that Pfizer has a hole to fill, following speculation that Revolution Medicines is an acquisition target of other big pharmas. However, a closer look at Pfizer’s pipeline shows that the group already has another pan-KRAS in phase 1, PF-07934040 – and the company has confirmed to ApexOnco that this remains in development.

Pfizer blamed "business reasons" for the latest decisions, saying they weren't spurred by any safety concerns, regulatory agency requests, or study conduct issues. The discontinuations came to light after study recruitment targets were slashed and their statuses were changed from “recruiting” to “active, not recruiting” on clinicaltrials.gov.

Next gen?

Curiously the discontinued '045, which went into phase 1 in December 2024, was billed in Pfizer’s pipeline as a “next-generation” project, while the first-gen '040, which entered human testing in June 2024, remains.

It’s unclear exactly how the two projects differ. '040's phase 1 trial is due to complete next year, according to clinicaltrials.gov.

Broadly targeting KRAS, and RAS, has become increasingly hot, with the leader in this space, Revolution, linked with rumours of a buyout by AbbVie – which that group denied – and then Merck & Co. However, the JP Morgan healthcare conference came and went with no deal emerging.

Plenty of others are getting into the area, with AstraZeneca recently striking a much smaller $100m deal with Jacobio over JAB-23E73. It's still an open question whether targeting KRAS, versus RAS, makes a difference.

ISAC woes

There are fewer PD-L1-targeting ADCs, and now there are fewer still with the demise of Pfizer's '037. However, that project had a somewhat unusual design, being an immune-stimulating antibody conjugate (ISAC) that used a toll-like receptor 7 (TLR7) agonist as a payload.

Other groups taking a similar approach have also faltered, including Bolt Therapeutics, which first scrapped the HER2-targeting trastuzumab imbotolimod, and then saw strong immune responses with the Claudin18.2-targeting BDC-4182 that spurred it to introduce step-up dosing.

It’s unclear whether Pfizer had similar problems finding a therapeutic window for '037, but at least the company still has the Seagen-originated fetrastobart vedotin, which uses a tried-and-trusted vedotin payload. In September, that project started a phase 3 trial in post-PD-(L)1 NSCLC, versus docetaxel; however, Pfizer disclosed in November that it was no longer going to start a planned pivotal study of fetra-v in first-line head and neck cancer.

Pfizer also recently canned the mesothelin-targeting ADC PF-08052666, marking the latest failure in this arena.

Pfizer's recent discontinuations

Project	Description	Status
PF-07985045	“Next-gen” pan-KRAS inhibitor	Ph1 trial recruitment reduced from 190 to 26, marked as “active, not recruiting”
PF-08046037	Anti-PD-L1 ISAC (TLR7 agonist payload)	Ph1 trial recruitment reduced from 399 to 9, marked as “active, not recruiting”
PF-08052666	Mesothelin-targeting ADC (topo1 inhibitor payload)	Ph1 trial recruitment reduced from 365 to 19, marked as “active, not recruiting”