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.|