J&J’s bispecific wins first approval for exon 20 lung cancer niche

Swift approval for amivantamab, now trademarked Rybrevant, gives J&J first crack at non-small cell lung cancer driven by exon 20 insertions, a hard-to-treat subset. The accelerated approval comes two months before the FDA’s goal, and was based on data presented at World Lung earlier this year that included a 40% response rate. Developers have previously struggled to hit this mutation effectively with small molecules; Rybrevant is notable for being a bispecific against EGFR and Met. Rybrevant’s infused administration could become a hindrance, a theory that might be tested should Takeda’s small molecule mobocertinib win approval by its October 26 Pdufa date. Mobocertinib data at World Lung were arguably less impressive than Rybrevant’s, although the evidence for both is likely to evolve. Spectrum seems to have restricted its work with poziotinib to Her2 exon 20 mutations, which would not make it a direct competitor. Otherwise the pipeline includes a couple of projects in development in China, and BDTX-189 from Black Diamond, which underwhelmed last week with data due to be presented at Asco next month. Cullinan is also presenting an update, on CLN-081, at the conference.

Notable ongoing studies in EGFR/Her2 exon 20 mutations 
Project Mechanism Sponsor/Collaborators Trial name/NCT ID Trial description 
Rybrevant EGFR-Met bispecific antibody J&J Papillon  Ph3 1st-line confirmatory study
  J&J  Chrysalis  Ph1 with exon 20 cohort in relapsed NSCLC
EGFR/Her2 exon 20 kinase inhibitor Takeda NCT04129502 Ph3 1st-line study 
  Takeda NCT02716116 Ph1/2; 1st and 2nd-line NSCLC with EGFR or Her2 exon 20 
Poziotinib EGFR/Her2 exon 20 kinase inhibitor Spectrum  Zenith20 Ph2 (open label); 1st and 2nd line study 
BDTX-189 TKI targeting all EGFR/Her2 mutations Black Diamond Therapeutics MasterKey-01 Ph1 trial with cohorts of several EGFR or Her mutations; data at Asco
JMT101 Anti-EGFR MAb Shanghai JMT-Bio  NCT04448379 Phase 1b in exon 20
CLN-081 EGFR exon 20 kinase inhibitor Cullinan Oncology NCT04036682 Ph1/2 in EGFR exon 20; data at Asco  
DZD9008 EGFR/Her2 exon 20 kinase inhibitor Dizal Pharmaceuticals NCT03974022 Ph1/2 in EGFR exon 20/Her2 mutations
Tarloxotinib bromide Pan-ErbB inhibitor Rain Therapeutics  NCT03805841 Ph2; exon 20 Her2-activating mutations, other NRG1/ERBB gene fusions; asset possibly deprioritised
Source: clinicaltrials.gov & Evaluate Pharma

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