Another B7-H3 death puts Imdelltra combo in trouble

Shortly after Amgen and Zai Lab struck a curious clinical trial collaboration to combine their respective DLL3-targeting projects, Imdelltra and zocilurtatug pelitecan, the plan to test Imdelltra combinations has run into difficulties. That’s become evident from another combo, testing Imdelltra with MediLink’s anti-B7-H3 ADC tambotatug pelitecan, whose phase 1 Dellphi-310 study has gone on hold owing to a “fatal pneumonitis event”, according to an update on the EU trials registry. The obvious connection here is with another anti-B7-H3 ADC, Daiichi Sankyo/Merck & Co’s ifinatamab deruxtecan, which spent time on clinical hold owing to deaths from interstitial lung disease. But a less obvious one is that tambota-P and Zai’s zoci-P both use MediLink’s vaunted Tmalin linker technology, and employ an identical topoisomerase inhibitor payload. It’s not clear whether there might be any class effect here, and Zai’s combo plan was followed up on Wednesday with an equally curious collaboration, seeking to test zoci-P with Boehringer Ingelheim’s anti-DLL3 T-cell engager obrixtamig. Dellphi-310 is sponsored by Amgen, which has issued no statement about its hold, presumably because this is temporary and apparently limited to six EU countries. MediLink licensed tambota-P to Roche in January.

Selected studies

Source: OncologyPipeline.