AACR 2026 – one more shot for integrins

While efforts to target integrins have largely fallen short, Pliant Therapeutics is hoping to turn the tide. It's one of the few clinical-stage companies still pursuing these targets, and AACR could be the moment it shows why its approach might succeed where others have struggled. 

The conference will also introduce the first data from some new contenders. This is the case of Abogen's ABO2203, an mRNA-encoded T-cell engager, and Tavotek's TAVO412, a trispecific antibody that targets EGFR, cMet and VEGF, the first asset to combine all three in a single molecule. 

Integrins' last chance?

Pliant’s PLN-101095 is the last clinical-stage integrin avβ8 inhibitor remaining, following recent setbacks for projects from Corbus Pharmaceuticals and Pfizer.

However, Corbus’s CRB-601 and Pfizer’s PF-06940434 were MAbs, whereas Pliant’s project is a small-molecule inhibitor of αvβ8 and αvβ1. Full data are due at AACR from a phase 1 trial testing monotherapy or a Keytruda combo in post-Keytruda solid tumours.

In December four responses (one complete) were reported among 10 immune checkpoint-refractory patients given the three highest doses combined with Keytruda. One of these responses was unconfirmed, but Pliant also pointed to large increases in plasma interferon gamma among responders, something that wasn’t seen in non-responders. This biomarker might come under the spotlight at AACR.

Pliant is already planning a phase 1b expansion trial in NSCLC, clear cell renal cell carcinoma and tumours with high tumour mutational burden. 

Degraders & PARP1 inhibitors

Degraders are hot right now, but Captor Therapeutics’ CT-01 (CPT-6281) is unusual in that it takes aim at not just one but three targets: GSPT1, SALL4 and NEK7. A phase 1 trial tests the project, with or without everolimus, in patients with second-line or later liver cancer. No results have yet been reported.

OncologyPipeline shows no direct rivals to CT-01, although there are plenty of GSPT1 degraders, of which the most advanced is Monte Rosa Therapeutics, which has said it plans to start a phase 2 study of MRT-2359 this year. Gyre also recently bought Cullgen for its degraders, including the GSPT1-targeting CG009301. Meanwhile, there are no other SALL4 or NEK7 degraders in development.

At the same time, PARP1 inhibitor development is also moving forward, with new phase 1/2, late-line, solid tumour trial data for ACE-86225106 (ACE-106) from Acerand. Early results were presented at last year’s ASCO meeting, showing three partial responses among 13 patients across four doses: 5mg, 10mg, 20mg and 30mg. Two responders had prostate cancer, and one had fallopian tube cancer.

The most advanced PARP1 inhibitor is AstraZeneca’s saruparib, in phase 3 in high-risk localised and hormone-sensitive prostate cancer, and first-line breast cancer.

First clinical data

In a separate oncology development, Tavotek Lab appears to want to improve on Johnson & Johnson’s Rybrevant with TAVO412, a trispecific antibody targeting EGFR, c-Met, and VEGF. The project is in two phase 1 trials, one in China and one in the US, in solid tumours including gastric and non-small cell lung cancers. AACR looks set to be the first venue for results on this asset. 

There are no similarly acting projects in development, according to OncologyPipeline. Rybrevant, which targets EGFR and cMet, is FDA-approved in various EGFR-mutated NSCLC settings. Companies developing cMet x VEGF bispecifics include Nanchang Hongyi, which is developing LMV-12.

And, on the bispecific front, mRNA-encoded T-cell engagers have so far been the domain of Moderna and BioNTech, but another contender will emerge at AACR, with the first clinical data on Suzhou Abogen’s ABO2203. The project, which aims to spur patients to develop their own CD19-targeting T-cell engagers, is in a Chinese phase 1 trial for relapsed/refractory B-cell lymphoma.

ABO2203 might have to match Amgen’s approved therapy Blincyto, although that uses a protein fragment rather than a full antibody. Competition could also come from the likes of Merck & Co’s MK-1045, acquired via its purchase of Curon, and AstraZeneca’s surovatamig, which recently entered phase 3.

Meanwhile, BioNTech reckons it’s shown proof of concept with its mRNA-encoded T-cell engager BNT142, which targets Claudin6, although response rates were lacklustre. Moderna, meanwhile, is developing mRNA-2808 in multiple myeloma; this project encodes three T-cell engagers, thought to target BCMA, FcRH5 and GPRC5D. 

Selected AACR oral clinical trial presentations

AACR 2026 takes place in San Diego on 17-22 April.