China-based InnoCare has opened a third Phase III study of mesutoclax, a homegrown Bcl-2 inhibitor, as a 318-patient, randomised, multicentre, open-label trial testing mesutoclax plus azacitidine versus venetoclax plus azacitidine in elderly or unfit treatment-naive acute myeloid leukaemia (AML), with overall survival as the primary endpoint.

The head-to-head design is the headline: rather than benchmarking against placebo or historical data, InnoCare is challenging AbbVie/Genentech's venetoclax + azacitidine standard directly, while the company's other two Phase III programmes pair mesutoclax with orelabrutinib in relapsed or refractory mantle cell lymphoma (r/r MCL) and treatment-naive chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma.

The Phase I ICP-CL-01205 signal justifies the ambition: 81.8% of treatment-naive AML patients achieved complete response or complete response with incomplete haematologic recovery, 86.5% were MRD negative and 83% of complete responders did so in cycle one, while the 125 mg cohort showed 93.3% six-month duration-of-response and 90.5% six-month survival, and TP53-mutant patients posted a 71.4% complete-response rate (CRR).