Roche follows Pfizer out of LTβR
The group also discontinues a mystery asset, and a Tecentriq trial in periadjuvant lung cancer.
The group also discontinues a mystery asset, and a Tecentriq trial in periadjuvant lung cancer.
The LTβR pipeline is looking bare, after Roche disclosed on Thursday that it had discontinued RG6221, a bispecific project also targeting FAP. The move comes just over a year after Pfizer ended a phase 1 trial of its rival LTβR agonist PF-07329640, and a look at OncologyPipeline shows only a couple of active projects in very early development.
Roche also ended another phase 1 asset, RG6561, but details on this are scarce, with its mechanism undisclosed. In addition, the Swiss group removed a Tecentriq trial in periadjuvant NSCLC from its phase 3 pipeline; this looks likely to be Impower-030.
Lacklustre LTβR
LTβR (lymphotoxin-β receptor) is a member of the tumour necrosis factor receptor superfamily, and agonists such as RG6221 and PF-07329640 were said to induce tertiary lymphoid structure formation, aggregates of cancer-fighting immune cells.
While Pfizer’s project was a tetravalent antibody, RG6221 was a bispecific MAb that also bound to fibroblast activation protein (FAP). By targeting FAP, Roche’s project was designed to agonise LTβR only in the tumour microenvironment, thereby avoiding widespread LTβR activation and minimising toxicity.
Still, this approach doesn’t seem to have worked, either. Late last year Roche cahnged the status of a phase 1 solid tumour trial testing RG6221 with or without Tecentriq, from “recruiting” to “active, not recruiting”, after this enrolled just 34 out of a planned 180 patients – a sure sign that things weren’t going to plan.
And on Thursday the group confirmed the project was on the scrapheap. Meanwhile, Pfizer doesn’t appear to have formally discontinued PF-07329640, but hopes aren’t high after the group terminated a phase 1 study in late 2024 for “business reasons”.
The latest news could be a worry to Mestag Therapeutics, whose MST-0300 also targets both LTβR and FAP; an IND is expected in early 2026. NGM is taking a different tumour-anchoring approach with ABX4233, using B7-H4 to target LTβR activity, but that project looks to be even earlier in development.
Industry projects with activity at LTβR
| Project | Mechanism | Company | Note |
|---|---|---|---|
| RG6221 (RO7567132) | LTβR x FAP bispecific MAb | Roche | Discontinued Jan 2026; ph1 solid tumour trial marked “actve, not recruiting” in Dec 2025, after enrolling 34 of 180 patients |
| PF-07329640 | LTβR agonist tetravalent MAb | Pfizer | Ph1 solid tumour trial discontinued Nov 2024; no further development, assumed abandoned |
| MST-0300 | LTβR x FAP bispecific MAb | Mestag Therapeutics | Preclinical; IND due “early” 2026 |
| ABX4233 | LTβR x B7-H4 bispecific MAb | NGM Bio | Preclinical data at AACR 2025 |
Source: OncologyPipeline.
Meanwhile, Tecentriq has lagged behind its PD-(L)1 rivals in periadjuvant NSCLC; Merck & Co’s Keytruda got FDA approval here in October 2023, based on Keynote-671, followed by AstraZeneca’s Imfinzi in August 2024 (based on Aegean), and Bristol Myers Squibb’s Opdivo in October the same year (Checkmate-77T).
All are indicated in combination with chemo in the neoadjuvant treatment phase, followed by adjuvant monotherapy. Roche was taking a similar approach with Impower-030, which completed in October, and which seems likely to be the study just revealed to have been discontinued.
The Swiss company didn’t give any reasons for this in its presentation, but perhaps Tecentriq didn’t look sufficiently different from the competition. The drug is approved in NSCLC, including as adjuvant therapy, but the news will do nothing to change its perception as a PD-(L)1 also-ran.
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