ASCO-GI – Inhibrx presses ahead with DR5

One of the few remaining industry projects targeting DR5, Inhibrx's ozekibart, has shown some promise in relapsed colorectal cancer. Targeting DR5 is notoriously difficult, having seen off IGM Biosciences' aplitabart and several clinical-stage assets, and the ozekibart data, from a phase 1 solid tumour cohort presented at the ASCO Gastrointestinal Cancers symposium, aren't without flaws. The abstract reports four partial responses among 13 patients given ozekibart plus Folfiri, for a 31% ORR at a 9 August 2024 cutoff; but 31% of patients experienced severe ozekibart-related adverse events, and there was one death, from neutropenic sepsis. Ozekibart is a tetravalent MAb designed to increase DR5 clustering, something others have tried to achieve through bispecific approaches hitting DR5 plus CEA, MUC16, CDH17 or FAP. Monospecifics included two projects terminated by Daiichi Sankyo, and multispecifics too have struggled: among others Genmab terminated GEN1029, and Roche gave up on RO6874813. Ozekibart is separately in phase 2 in chondrosarcoma. For its part IGM also studied aplitabart plus Folfiri in colorectal cancer, but last September turned away from oncology to autoimmune disease; two weeks ago it admitted that it couldn't compete in autoimmune disease either, and scrapped two projects plus 73% of its workforce.

Selected projects targeting DR5 (TRAIL-R2)

Source: OncologyPipeline.