Glaxo follows Jounce with an Icos setback

Glaxosmithkline’s efforts to make progress in oncology have taken another knock with the discontinuation of two phase 3 trials of its Icos agonist feladilimab. The studies in question are in head and neck cancer in combination with Merck & Co’s Keytruda: Induce-3 is in PD-L1-positive subjects, while Induce-4, in all-comers, additionally gives chemo. Two remaining phase 2 tests continue, but must now also be seen as highly speculative; one combines feladilimab with Astrazeneca’s tremelimumab and the other includes Bristol Myers Squibb’s Yervoy. The CTLA-4 combo strategy was seriously undermined with last year’s failure of the Emerge study of Jounce’s competing Icos MAb vopratelimab plus Yervoy (Jounce trounced after Icos stumble, November 3, 2020). If the latest setbacks signal the end of feladilimab – the industry’s most advanced Icos MAb – this will add to Glaxo’s struggles in oncology. The group’s anti-BCMA ADC Blenrep did make it across the line in multiple myeloma, but toxicity looks set to limit its use to late-line settings; the anti-PD-(L)1 MAb dostarlimab is still not approved in the US, after a 2020 Pdufa date came and went; and another once-promising late-stage asset, bintrafusp alfa, has failed two important studies.

What next for Icos?
Project Company Mechanism Status
Feladilimab (GSK3359609) Glaxosmithkline Icos agonist MAb Ph3 Induce-3 & Induce-4 (Keytruda combos) discontinued; ph2 anti-CTLA-4 combos ongoing
Vopratelimab (JTX-2011) Jounce Therapeutics Icos agonist MAb Ph2 Emerge (Yervoy combo) failed; ph2 Select (JTX-4014 combo) ongoing
BMS-986226 Bristol-Myers Squibb Icos agonist MAb Phase 1/2 (Opdivo/Yervoy combo) ends Oct 2022
XmAb23104 Xencor Icos co-stimulator x anti-PD-1 bispecific MAb Ph1 Duet-3 (Yervoy combo) ends Sep 2024
Autoimmune disease
ALPN-101 Alpine Immune Sciences/Abbvie Icos/CD28 antagonist Ph1 GvHD study terminated; ph2 in lupus starts Jul 2021
MEDI-570 Astrazeneca Anti-Icos MAb Discontinued in ph1 (lupus)
Source: company information &

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