Merck and Daiichi look for more ifinatamab white space

Development of B7-H3 ADCs has so far largely focused on small-cell lung cancer, but Merck & Co and Daiichi Sankyo are going broader with their contender, ifinatamab deruxtecan. A Merck-sponsored phase 3 in relapsed metastatic castrate-resistant prostate cancer will start next month, according to a recent listing on clinicaltrials.gov – adding to ongoing Daiichi-led pivotal studies in second-line SCLC and oesophageal cancer. The new trial, Ideate-Prostate01, will test ifinatamab-dxd versus docetaxel and prednisone, with co-primary endpoints of radiographic progression-free survival and overall survival. Daiichi previously reported a 25% overall response rate among 59 late-line mCRPC patients in its phase 1/2 Ideate-Pantumor01 trial. The partners are ahead of the pack here, with development of other B7-H3 ADCs in CRPC limited to phase 2. And MacroGenics recently discontinued vobramitamab duocarmazine after seeing treatment-related deaths in the Tamarack study – although efficacy looked positive. Vobra-duo used a DNA alkylating agent payload, so Merck and Daiichi will hope to avoid similar issues with ifinatamab-dxd, which employs a topoisomerase 1 inhibitor, as do projects from GSK/Hansoh and MediLink. More B7-H3 competition could come from BioNTech/DualityBio’s BNT324, although the German group is currently focusing on lung cancers and a combination with its PD-L1 x VEGF bispecific antibody BNT327.

B7-H3 ADCs in second-line mCRPC

Source: OncologyPipeline & clinicaltrials.gov.