Ominous signs for EGFR degraders

Since EGFR degraders first emerged there has been little news, but what is now surfacing isn’t encouraging. Last week BeOne’s phase 1 trial of BG-60366, evaluating the EGFR degrader in patients with advanced or metastatic EGFR-mutant non-small cell lung cancer, was listed as “active, not recruiting” on clinicaltrials.gov, with enrolment halted at 33 patients, well short of the 93 originally planned. When asked about the shift, a BeOne spokesperson said the study "has been paused while we evaluate the available study data". Although the company has not officially confirmed discontinuation, the outlook for BG-60366 is increasingly uncertain, casting doubt over the future of this asset.There's been no indication as to what in the emerging data might have prompted BeOne to pause the trial in this way, but the potential emergence of an adverse event can't be ruled out.EGFR degradersAs for other assets with the same mechanism of action, updates remain sparse. According to OncologyPipeline there are four other EGFR degraders currently in clinical development, but none has yielded results so far.HSK40118 from Haisco Pharmaceuticals is an EGFR-mutant degrader that has been in the clinic since 2023 for the treatment of lung cancer. C4 Therapeutics' CFT8919, meanwhile, only targets L858R mutations, and the latest update from the company, in February, was that it would use data from its China trial to inform development outside China. This was expected for the end of the first quarter, though no updates have been disclosed.  There are also two projects from Jing Medicine Technology: HJ-002-03 and HJ-004-02. The latter is the latest to enter clinical trials. Next RybrevantMeanwhile, BeOne appears to be shifting its EGFR focus, and is attempting to develop two assets, BG-T187 and BG-C0902, that owing to their mechanisms could rival Johnson & Johnson’s Rybrevant. The first is a trispecific antibody targeting EGFR and two distinct epitopes of cMet, while the second is an antibody-drug conjugate combining the trispecific antibody with a topoisomerase 1 inhibitor. Selected EGFR degradersProjectCompanyMechanism of actionStatusHSK40118Haisco PharmaceuticalEGFR mutant degraderPhase 1 in NSCLC ongoingCFT8919C4 TherapeuticsEGFR L858R degraderPhase 1 in NSCLC ongoingHJ-004-02Jing Medicine TechnologyEGFR degraderPhase 1 in NSCLC ongoingHJ-002-03Jing Medicine TechnologyEGFR degraderPhase 1 in NSCLC ongoing BG-60366BeOneEGFR mutant degraderPhase 1 trial listed as "active, not recruiting" in Apr 2026; enrolment halted at 33 patientsSource: OncologyPipeline.