Roche sounds another warning over co-stimulation

Co-stimulatory approaches have previously run into difficulties, and the latest group to throw in the towel is Roche. The company noted in its first-quarter presentation that it has discontinued the 4-1BB co-stimulated anti-CD19 antibody-fusion protein englumafusp alfa, which had been in phase 1 in relapsed/refractory B-cell non-Hodgkin’s lymphoma.

The company didn’t give a reason for the discontinuation, but it will be noted by others pursuing non-cell therapy approaches to hitting CD19, such as AstraZeneca with surovatamig and Merck & Co with the Curon-originated MK-1045. Those are both T-cell engagers, making them distinct from englumafusp alfa.

As for attempts to harness co-stimulatory domains, a big casualty was the anti-PD-L1 x 4-1BB project acasunlimab, which Genmab quietly dropped at the end of last year, after losing BioNTech as a partner only a few months before. Another co-stimulatory approach involves using CD28, where Regeneron has been particularly active.

Roche’s latest move will only add to the broad doubts around that have already arisen in this field. The company’s only other 4-1BB project, according to OncologyPipeline, is clesitamig, a trispecific T-cell engager that also targets DLL3 and is in phase 1 in small-cell lung cancer.

New mystery project

Meanwhile, Roche disclosed that another asset, RG6735, was entering phase 1 in blood cancers, but details were scant. It’s possible that this has a different code, but with the Swiss group not disclosing the project’s mechanism there’s not much to go on. Maybe more information will emerge in its clinicaltrials.gov listing.

Roche also confirmed that it’s filed Lunsumio plus Polivy in second-line DLBCL, based on the Sunmo trial. The study could be controversial, with only 10% of patients coming from North America, and the FDA knocked back Roche’s Columvi in second-line DLBCL after a similar issue with the Starglo study, which the agency deemed wasn’t applicable to the US population.

In addition, the company has filed its SERD giredestrant in adjuvant breast cancer, based on the Lidera trial; here it used a priority review voucher to speed things up. Giredestrant is awaiting an FDA approval decision in second-line breast cancer by 18 December.

In the last of its oncology pipeline updates, Roche highlighted a new phase 2 trial of Itovebi plus Xtandi in castration-resistant prostate cancer. The InavoPC study, in patients who have previously received an androgen receptor pathway inhibitor, started in March.

What’s in and out at Roche

Source: company Q1 2026 presentation.