China grants breakthrough status for InnoCare's orelabrutinib-mesutoclax combo in MZL

China-based InnoCare Pharma (HKEX: 09969; SSE: 688428) announced that its combination of orelabrutinib with mesutoclax has been granted Breakthrough Therapy Designation (BTD) by China's Center for Drug Evaluation (CDE). The award covers the regimen's potential as a treatment for marginal zone lymphoma (MZL) in patients who have received at least one prior therapy. Orelabrutinib is a selective oral Bruton's tyrosine kinase (BTK) inhibitor, and mesutoclax (ICP-248) is an oral BCL2 inhibitor that restores apoptosis in cancer cells by selectively inhibiting BCL2 protein.

The designation was supported by data presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting from a Phase I/II dose-escalation and expansion study in patients with relapsed or refractory MZL who had received at least one prior therapy. The combination achieved an overall response rate (ORR) of 100% in this population, with a complete response rate (CRR) of 50% in patients with at least one disease evaluation receiving mesutoclax 125 mg in combination with orelabrutinib. No treatment-emergent adverse events (TEAEs) leading to drug discontinuation or death were reported across the B-cell malignancy groups evaluated.

This is the second BTD granted to mesutoclax by the NMPA. The first designation, awarded in May 2025, covered BTKi-treated relapsed or refractory mantle cell lymphoma (MCL), making mesutoclax the first BCL2 inhibitor to receive BTD recognition in China. InnoCare's orelabrutinib is already approved in China for relapsed or refractory MZL as a monotherapy, and the BTD for the combination opens an accelerated development pathway for a chemo-free doublet in the same indication.

The BTD will allow InnoCare to pursue an expedited registrational pathway for the combination in MZL in China. A Phase III registrational trial of mesutoclax in combination with orelabrutinib for first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has already completed patient enrollment in China, and a registrational study in BTKi-treated MCL is advancing. The MZL BTD adds a third indication pathway for the combination, broadening the potential commercial scope of mesutoclax within InnoCare's hematology franchise.

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