Corbus joins Pfizer with integrin no-go

Corbus Pharmaceuticals, whose oncology work is best known for an antibody-drug conjugate against Nectin-4, looks set to remain primarily focused on this asset. That’s become apparent after the deprioritisation of the biotech’s second anticancer project, CRB-601.

The move, disclosed in Corbus’s fourth-quarter report, spells the likely end of CRB-601, a MAb that targets integrin avβ8; though CRB-601 hasn’t formally been discontinued, and its phase 1 study remains active, it’s been removed from Corbus’s R&D pipeline. Notably, the other key anti-integrin avβ8 contender, Pfizer’s PF-06940434, had its phase 1 study terminated a year ago.

No clinical efficacy data were reported on either CRB-601 or PF-06940434. The Corbus project was profiled in a “study in progress” poster at last year’s SITC conference, but this only disclosed safety: among 25 patients grade 3 treatment-emergent adverse events were reported in eight, with only one event, pruritus, deemed related to CRB-601.

Show me

In previous communication with ApexOnco Corbus had described the anti-integrin avβ8 mechanism as a “show me” story. According to its fourth-quarter report the company now doesn’t plan to enrol additional patients into its phase 1 study of CRB-601 in advanced solid tumours known to express avβ8. 

Pfizer also hadn’t reported any clinical data on PF-06940434, though it's understood to have completed phase 1 dose expansion just over a year ago. But that study was marked terminated in January 2025, with clinicaltrials.gov citing “strategic considerations and not due to specific safety reasons or a request from a regulatory authority” as the reason.

Integrin avβ8 was thought to be an interesting oncology target owing to its role in TGF-β activation, and its perceived potential irrespective of tumours’ PD-L1 sensitivity. TGF-β is associated with promoting immune exclusion in the tumour microenvironment, and thus resistance to checkpoint inhibitors, but exists in a latent form before its activation.

It’s understood that some monotherapy activity was needed as a gating factor for taking CRB-601 forward, but apparently no meaningful effect was seen. Corbus told ApexOnco that it now saw CRB-701, its anti-Nectin-4 ADC, as more worthy of its focus, though it does plan to publish preclinical and clinical data on CRB-601 at some point.

Corbus licensed rights to develop CRB-601 from University of California San Francisco in mid-2021, at the same time as licensing a separate MAb, blocking αvβ6/αvβ8, from Panorama Research. Interestingly, PF-06940434 is also understood to have been based on work conducted at UCSF, though at a separate lab.

Industry work on integrin αvβ8

Source: OncologyPipeline.

The effective discontinuations of first PF-06940434 and now CRB-601 leave Pliant Therapeutics as the last player standing with a clinical-stage project that inhibits αvβ8, according to OncologyPipeline.

However, Pliant’s PLN-101095 isn’t a MAb but a small-molecule, which inhibits αvβ1 as well as αvβ8. It started a first-in-human study back in August 2023, since when a couple of promising signals of clinical activity have been reported: a year ago Pliant claimed three confirmed partial responses among six patients given PLN-101095 at 1g twice daily.

Then, last December, four responses (one complete) were reported among 10 immune checkpoint-refractory patients given the three highest doses combined with Keytruda. Pliant says it will begin phase 1b dose expansion this year.

With questions hanging over the αvβ8 mechanism it’s also worth noting the setback of another approach at blocking the activation of latent TGF-β, namely GARP blockade: AbbVie’s anti-GARP MAb livmoniplimab recently hit a dead end in phase 2/3.