China’s NMPA approved InnoCare’s Phase III trial of mesutoclax plus azacitidine versus venetoclax plus azacitidine in treatment-naive AML
Written By: Siddhi Bhadekar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
InnoCare Pharma has received approval from China’s National Medical Products Administration (NMPA) to conduct a registrational Phase III trial (NCT06656494) evaluating its BCL2 inhibitor mesutoclax (ICP-248) in combination with azacitidine against venetoclax plus azacitidine in treatment-naive patients with acute myeloid leukemia (AML) who are elderly or ineligible for intensive chemotherapy.
The study will directly compare mesutoclax with an established first-line treatment option in this patient population. The development decision follows early efficacy and safety findings from a Phase I combination study of mesutoclax and azacitidine, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.
Regulatory Approval Establishes a Head-to-Head Registrational Design
China’s Center for Drug Evaluation (CDE), operating under the NMPA, has cleared InnoCare to launch a registrational Phase III study comparing mesutoclax with venetoclax, with azacitidine used as the backbone treatment in both arms.
The trial will enroll treatment-naive AML patients who are elderly or ineligible for intensive chemotherapy and will use a randomized, open-label, multicenter design. Overall survival is the primary endpoint. By using an active comparator rather than placebo, the study is designed to determine whether mesutoclax can improve outcomes compared with venetoclax plus azacitidine in this setting.
Early Efficacy Signals Behind the Phase III Program
The decision to advance mesutoclax into a head-to-head registrational study follows results from an earlier-stage study evaluating mesutoclax in combination with azacitidine. In the data presented at the 2026 ASCO Annual Meeting, 81.8% of evaluable treatment-naive AML patients achieved composite complete remission (CR plus CRi).
Among the reported study population, 86.5% achieved measurable residual disease (MRD) negativity, and most complete responders reached this status within a single treatment cycle, indicating that deep responses could occur early during treatment.
No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. Thirty-day and 60-day mortality were both reported as zero. In the 125 mg mesutoclax group, the six-month overall survival rate was 90.5%, while the six-month duration-of-response rate was 93.3%.
These findings provide the clinical rationale for further evaluation, but the early-stage data do not establish superiority or clinical differentiation from venetoclax. The randomized Phase III study will be required to determine whether mesutoclax provides a meaningful clinical benefit over the established comparator regimen.
Mechanism of Action: Selective BCL2 Inhibition
Mesutoclax is an oral, selective inhibitor of BCL2, a protein that helps leukemia cells evade programmed cell death. By inhibiting BCL2, mesutoclax is designed to restore apoptotic signaling and promote the death of malignant cells.
Mesutoclax and venetoclax therefore belong to the same pharmacological class. The head-to-head Phase III study will provide a direct clinical assessment of whether mesutoclax can improve outcomes compared with venetoclax when both are administered with azacitidine.
Company Perspective on Global Clinical Development
Dr. Jasmine Cui, InnoCare’s co-founder, chairwoman and chief executive officer, said the efficacy and safety data generated to date gave the company confidence to evaluate mesutoclax directly against an established standard treatment. She described mesutoclax as one of InnoCare’s key global assets.
According to the company, development of the mesutoclax-azacitidine combination is also progressing internationally, with patients enrolled in the United States and Australia alongside the newly approved China program. InnoCare said it intends to continue advancing the program toward broader patient populations worldwide.
Regulatory Designations Across the Mesutoclax Program
Mesutoclax has previously received Breakthrough Therapy Designation from China’s CDE, reflecting regulatory recognition of its potential in an area of significant unmet medical need. The newly approved head-to-head Phase III study is intended to generate registrational evidence directly against an established treatment regimen.
Disease Context: Treatment Considerations in Elderly and Unfit AML Patients
AML is a hematologic malignancy arising from abnormal blood-forming cells, and its incidence increases with age. Many older patients and those who are medically ineligible cannot tolerate intensive induction chemotherapy, making less-intensive treatment approaches important in this population.
Azacitidine and other hypomethylating agents combined with a BCL2 inhibitor have become important treatment approaches for patients with newly diagnosed AML who are not candidates for intensive chemotherapy. By comparing mesutoclax plus azacitidine directly with venetoclax plus azacitidine, the Phase III program is designed to determine whether the investigational BCL2 inhibitor can improve clinical outcomes in this treatment setting.
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About the Writer
Siddhi Rajendra Bhadekar (Linkedin) is an M.Pharm professional with expertise in medical and scientific writing, literature review, publication writing, and evidence synthesis, supported by four peer-reviewed publications.
She brings working knowledge of ICH-GCP, MedDRA, pharmacovigilance, ADR/AE reporting, clinical data management, and regulatory documentation.
With experience across pharmaceutical R&D, Quality Control, and Quality Assurance, she combines scientific research skills with strong attention to accuracy and detail.
Her background in manuscript development, publication planning, and scientific communication enables her to translate complex healthcare information into clear, reliable content.