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
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
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,, company statements & Evaluate Pharma.

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