Cullinan bids to upstage Takeda and J&J

The slightly obscure niche of EGFR exon 20 insertions in lung cancer recently saw its first two drug approvals, and now a third company, Cullinan Oncology, wants a slice of the action. A phase 1/2 trial of Cullinan’s CLN-081 now comprises 73 evaluable patients, and among 39 given 100mg twice daily has yielded a 41% confirmed remission rate, the group said yesterday; a further four responses are, and will remain, unconfirmed. 41% ORR compares favourably with Takeda’s approved small molecule Exkivity, whose label cites 28%, and is in line with Johnson & Johnson’s Rybrevant (40%), though the latter is an antibody. One advantage of CLN-081 is that it spares Her2 and wild-type EGFR, implying superior safety; Cullinan says it has seen no grade 3 or greater treatment-related diarrhoea or rash, adverse reactions that have troubled both the approved drugs. Cullinan’s trial specifies fasting conditions, and the FDA has additionally requested a 20-patient food effect study. The most noteworthy competitor behind CLN-081 is Dizal’s DZD9008, after Spectrum’s poziotinib failed in EGFR exon 20. Still, only 5% of NSCLC EGFR mutations are in exon 20, so the big question is how many players such a small market can support.