The sun sets on Icos

Yet more confirmation, as though any were needed, that Icos agonism is a non-starter in immuno-oncology came yesterday, with Jounce revealing the failure of Select, its PD-1 combo study. Select had tested the Icos agonist vopratelimab plus the anti-PD-1 MAb pimivalimab, versus pimivalimab alone, in immunotherapy-naive NSCLC. Even though patients had been preselected for an 18-gene RNA tumour inflammation biomarker that Jounce said predicted the emergence of Icos-high CD4+ T cells, Select failed to meet a predefined threshold for tumour shrinkage, and the overall response rate was 27% for the combo versus 25% for pimivalimab monotherapy. Last year vopratelimab failed in Emerge, a Yervoy combo study, and shortly afterwards GSK discontinued its own Icos asset, feladilimab. Bristol Myers Squibb’s BMS-986226 no longer appears in its pipeline, meaning that the last man standing is Xencor’s Icos/anti-PD-1 bispecific izuralimab. A phase 1 trial combining this with Yervoy is due to end next year.

Oncology projects with activity on Icos
Project Company Pharmacology Status
Izuralimab (XmAb23104) Xencor Icos x anti-PD-1 bispecific MAb Ph1 Duet-3 study (Yervoy combo) ends Jul 2023
Feladilimab (GSK3359609) GSK Icos agonist MAb Discontinued after failing in ph3 (Keytruda combo)
Vopratelimab (JTX-2011) Jounce Therapeutics Icos agonist MAb Failed ph2 Emerge (Yervoy combo) & Select (pimivalimab combo)
BMS-986226 Bristol Myers Squibb Icos agonist MAb Discontinued; ph1/2 trial completed, no data released
MEDI-570 Astrazeneca Anti-Icos MAb Discontinued; NIH-sponsored ph1 study in T-cell lymphoma
Source: Evaluate Pharma & company information.

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