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 of this disease. The accelerated approval comes two months ahead of the FDA’s goal, and was based on data presented at World Lung earlier this year, which included a 40% response rate. Developers have previously struggled to hit this mutation effectively with small molecule kinase inhibitors; Rybrevant is notable for being a bispecific against EGFR and Met. Should an oral kinase inhibitor finally make it all the way, Rybrevant’s infused administration could become a hindrance, a theory that might be tested should Takeda’s mobocertinib win approval by its October 26 Pdufa date. Mobocertinib data was also at World Lung and was arguably less impressive than Rybrevant, although the evidence for both assets is likely to evolve as both remain under study. 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, meaning the field should get a better look at exon 20 assets coming behind Rybrevant.

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
Mobocertinib	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.  https://www.evaluate.com/vantage/articles/news/snippets/jjs-bispecific-wins-first-approval-exon-20-lung-cancer-niche