AbbVie scales back its GARP ambitions

AbbVie’s plan to push livmoniplimab aggressively into phase 3 on the basis of rather limited phase 1 backing seems to be unravelling. Three of four phase 2/3 trials of this anti-GARP antibody have dropped off the company’s pipeline listing, with no results reported, and the remaining study has halted recruitment after being significantly downsized.

Indeed, were it not for the fact that AbbVie still listed livmoniplimab as an active R&D project in a pipeline it published on 4 February, investors might logically assume that this project has been discontinued. AbbVie didn’t answer a request from ApexOnco to clarify the precise status either of livmoniplimab or of a BTK degrader coded ABBV-101, but the future of both looks in doubt.

AbbVie paid Argenx $40m up front for rights to livmoniplimab in 2016, when the project was still preclinical, but then took three years before starting phase 1. So it was a surprise when in 2024, after phase 1 showed livmoniplimab to be inactive as monotherapy, and to deliver underwhelming data as part of a budigalimab combo, the company revealed plans to take it straight into phase 3.

The late-stage studies that emerged all concerned combinations with budigalimab, AbbVie’s anti-PD-1 MAb. Two of the ones that have now apparently ended are Livigno-2 (phase 2/3) and Livigno-1 (phase 2), both in liver cancer.

AbbVie earlier said it expected to present data on both in 2025, but this didn’t materialise. Backing for this indication came from a phase 1 basket trial that showed a seemingly underwhelming 12% response rate. Not only that, but an expansion cohort had to be halted because of toxicity, so it might be that livmoniplimab simply didn’t have a therapeutic window.

GARP works as a docking receptor for latent TGF-β1, and is said to be expressed on T regulatory cells. Also gone, according to AbbVie’s fourth-quarter 2025 presentation, is a phase 2 urothelial bladder cancer trial, Livigno-3, for which there was slightly better backing in terms of efficacy, namely an 18% ORR in the same phase 1 study.

Last man standing

Unless AbbVie begins new clinical efforts these developments leave the phase 2/3 Livigno-4 study, in first-line lung cancer, as the last remaining chance for livmoniplimab.

That too appears doomed, however. It begun in April 2024 with an enrolment target of 840, but last month its staus on clinicaltrials.gov was changed from “recruiting” to “active, not recruiting”, after only 167 subjects had been enrolled. Similar trial registry changes made by Pfizer, Roche and Novartis have preceded project discontinuations.

There’s just a handful of other industry players pursuing GARP clinically, according to OncologyPipeline, of which perhaps the most notable is Daiichi Sankyo with DS-1055a.

Phase 2 & 3 studies of livmoniplimab

Note: *phase 2/3 trial; the others are phase 2. Source: OncologyPipeline.

Meanwhile, mystery surrounds a phase 1 BTK degrader project, ABBV-101, which AbbVie took into the clinic in 2023, and whose phase 1 trial ended last year with no data disclosed.

ABBV-101 still formally appears in AbbVie’s pipeline, but analysts at Evercore ISI on Wednesday reported that it had been discontinued. The Evercore analyst Gavin Clark-Gartner confirmed to ApexOnco that the company had told the bank in a post-presentation call that ABBV-101 was being discontinued in non-Hodgkin’s lymphoma.

It remains possible, of course, that AbbVie might in future pursue another indication such as chronic lymphoblastic leukaemia, the battleground for the two leading BTK degraders, BeOne’s BGB-16673 and Nurix’s bexobrutideg. However, BeOne and Nurix have both reported stellar data, so perhaps AbbVie decided that ABBV-101 couldn’t compete.