ADC Therapeutics has stopped development of lead solid tumor candidate ADCT-601. The biotech axed the AXL-directed antibody-drug conjugate (ADC) after failing to show a favorable benefit-risk profile in a phase 1b trial.
ADCT-601 consists of an anti-AXL antibody, licensed from BerGenBio, connected to a PBD-dimer toxin using linker technology from Synaffix. AXL is expressed in multiple tumor types, and high expression of the receptor often correlates to lower survival. Those properties have attracted multiple drug developers, but ADC identified its toxin and use of a biomarker assay in patient selection as differentiators.
The phase 1b trial represented an early test of whether those claimed advantages will translate into a compelling drug candidate. ADC provided an answer on Thursday, using its third-quarter results to drop ADCT-601 from its pipeline.
The biotech said it saw early signs of antitumor activity in the dose-escalation stage of the study. However, any optimism generated by those signs evaporated in the dose-optimization and expansion phase, when ADC was unable to demonstrate a favorable benefit-risk profile. The biotech said the clinical data and capital requirements for continued development led it to stop development.
ADC’s action ended the development of ADCT-601 as a single agent and combination therapy in sarcoma, pancreatic cancer and non-small cell lung cancer. The biotech is prioritizing its exatecan-based platform for solid tumors.
Exatecan, a potent inhibitor of topoisomerase I, is at the center of ADC’s next wave of candidates. The biotech has disclosed preclinical, exatecan-based ADCs against Claudin-6, NaPi2b, PSMA and ASCT2. The Claudin-6 and NaPi2b candidates were leading the way when ADC provided an update earlier in the year, having reached the IND-enabling stage ahead of the other two prospects.