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.

Therapy landscape for EGFR exon 20 insertion NSCLC
Asset	Company	Clinical trial/data
Approved
Rybrevant*	J&J	40% ORR (n=81), gr3/4 rash & diarrhoea at 4% & 3%
Exkivity	Takeda	28% ORR (n=114), gr3/4 rash & diarrhoea at 2% & 22%, warning of QTc prolongation
Investigational
CLN-081	Cullinan/Otsuka	ORR 37% (n=73), 41% at 100mg bid (n=39)
DZD9008	Dizal Pharmaceuticals	ORR 40% (n=53); trial also tests Her2 exon 20
BDTX-189	Black Diamond Therapeutics	1 PR in six evaluable EGFR or Her2 exon 20 subjects; development under review
JMT101**	Shanghai JMT-Bio	No clinical data
BLU-451/LNG-451	Blueprint (ex Lengo)	Ph1 starts Mar 2022
Nazartinib	Novartis	Showed preclinical potential in EGFR exon 20, but ph1/2 is in unspecified EGFR mutations
Poziotinib	Spectrum	Failed in EGFR exon 20; 24 Nov 2022 Pdufa date for Her2 exon 20 NSCLC
STX-EGFR-Exon20	Scorpion Therapeutics	Preclinical
Notes: *anti-EGFR-Met bispecific MAb; **anti-EGFR MAb; all others are small molecules. Source: Asco, clinicaltrials.gov, company statements & Evaluate Pharma. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/cullinan-bids-upstage-takeda-and-jj