SITC 2020 – Curevac is left carrying the Rig1 banner


Almost non-existent activity from Merck & Co’s Rig1 agonist MK-4621 makes it extremely unlikely that this project will go anywhere. Merck discloses little about phase I candidates, and has not mentioned MK-4621 for several years so it could already be abandoned. If so its late-breaking poster at SITC shows why: the extent of activity in a Keytruda combination trial was two partial responses among 30 patients, with one more after database cutoff; two responses were in patients with PD-L1-positive tumours, so it is hard to say which intervention was responsible. However, early results from a trial of Curevac’s Rig1 asset are slightly more encouraging, and with monotherapy data it is possible to argue that this project, CV8102, has some activity. Worrying toxicities included grade 3 liver enzyme elevation and pneumonitis with the highest dose, although the poster noted that the two highest-dose cohorts were still being expanded to determine what might be taken into phase II. Curevac has not yet made that decision – efficacy is far from persuasive – and it is notable that there are seemingly no other development efforts on this mechanism.

Responses to Rig1: phase I data in advanced solid tumours
  Single-agent responses  Anti-PD-1 combo responses   
CV8102  2 PRs, 1 CR that went on to relapse (n=29) 1 PR (n=21) NCT03291002
MK-4621 - 2 PR; +1 post database cutoff (n=30)  NCT03739138
Source: SITC 2020 posters.

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