Sonrotoclax Plus Azacitidine in Patients With MDS-IB2

NCT07885397 | Recruiting Phase 1

• 1 other identifier: SON-AZA-MDSIB2-2026
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 6

Brief Summary

This study will evaluate the safety and preliminary effectiveness of sonrotoclax combined with azacitidine in adults aged 18-70 years with newly diagnosed myelodysplastic neoplasms with increased blasts-2 (MDS-IB2). Sonrotoclax blocks BCL-2, a protein that helps cancer cells survive. Combining sonrotoclax with azacitidine may improve disease control. This study aims to determine whether the combination can induce remission with an acceptable safety profile, facilitate allogeneic stem cell transplantation in suitable patients, and improve long-term clinical outcomes. This multicenter, open-label study has two sequential parts. Phase Ib will evaluate different sonrotoclax doses and identify the recommended dose for phase II. Phase II will further assess remission rates and safety at the selected dose. All participants will receive sonrotoclax plus azacitidine; there is no randomized control group. Participants will undergo regular blood tests, bone marrow examinations, and monitoring for side effects. Suitable participants may proceed to transplantation based on disease response and clinical condition. Those who are not proceeding to transplantation and continue to benefit may continue treatment according to the protocol. Follow-up will assess the duration of remission, disease progression, subsequent treatment, survival, and quality of life.

Conditions

Myelodysplastic Syndromes, High Risk

Keywords

MDS-IB2; Sonrotoclax; Azacitidine

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicities (DLTs)

  Incidence of protocol-defined DLTs during the first treatment cycle.

  Cycle 1 Day 1 through Cycle 1 Day 28; up to Day 42 if required for assessment of unresolved hematologic toxicity.

• Maximum Tolerated Dose / Recommended Phase 2 Dose

  Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Sonrotoclax

  Through completion of the Phase Ib dose-escalation stage, approximately 12 months

• Composite Response Rate (CRR)

  Proportion of participants achieving complete remission (CR), complete remission with limited count recovery (CRL), or complete remission with partial hematologic recovery (CRh).

  From the first dose through completion of up to 4 treatment cycles, approximately 4 months

Secondary Outcomes (6)

• Duration of Response (DoR)

  Up to 36 months

• Measurable Residual Disease (MRD) Negativity Rate

  From baseline through the end of study treatment, up to approximately 12 months

• Progression-Free Survival (PFS)

  From the date of the first dose of study treatment to the date of the first documented disease progression, transformation to acute myeloid leukemia, or death from any cause, whichever occurs first, assessed up to 36 months.

• Overall Survival (OS)

  Up to 36 months

• Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) Rate

  Up to 36 months

Study Arms (1)

Sonrotoclax Plus Azacitidine

EXPERIMENTAL

Participants receive sonrotoclax in combination with azacitidine in 28-day cycles. Phase Ib evaluates sonrotoclax target doses of 40, 80, 160, and 320 mg daily using a modified dose-escalation design. Phase II evaluates the combination at the recommended phase II dose established after completion of phase Ib safety assessments. Treatment may continue according to protocol-defined response and safety criteria until disease progression, unacceptable toxicity, initiation of another anticancer treatment, transition to allogeneic hematopoietic stem cell transplantation, withdrawal of consent, or another protocol-defined stopping condition.

Drug: Sonrotoclax; Drug: Azacitidine (AZA)

Interventions

Sonrotoclax DRUG

Sonrotoclax is administered orally once daily. Phase Ib target doses are 40, 80, 160, and 320 mg; phase II uses the recommended phase II dose. In cycle 1, a four-day ramp-up administers one-eighth, one-quarter, one-half, and the full target dose on days 1, 2, 3, and 4, respectively. Treatment at the target dose is then continued for 14 days. From cycle 2 onward, sonrotoclax is generally administered on days 1-14 of each 28-day cycle. Dose interruptions, reductions, and adjustments to treatment duration or concomitant medications follow the protocol.

Also known as: BGB-11417

Sonrotoclax Plus Azacitidine

Azacitidine (AZA) DRUG

Azacitidine is administered at 75 mg/m² once daily by subcutaneous injection or intravenous infusion for seven consecutive days per 28-day cycle. In cycle 1, azacitidine is administered on days 4-10, beginning when sonrotoclax reaches its target dose. From cycle 2 onward, azacitidine is administered on days 1-7. Treatment delays and dose modifications are permitted according to protocol-defined toxicity and recovery criteria.

Sonrotoclax Plus Azacitidine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years, male or female.
• Voluntarily willing to participate in the study, able to understand and sign written informed consent, and willing to comply with study treatment, assessments, and follow-up.
• Newly diagnosed with myelodysplastic syndromes with increased blasts-2 (MDS-IB2) according to the current World Health Organization (WHO) diagnostic criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Estimated life expectancy of at least 12 weeks.
• Adequate organ function to tolerate study treatment, including:
• Total bilirubin ≤1.5 × upper limit of normal (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN;
• Creatinine clearance ≥40 mL/min;
• Left ventricular ejection fraction (LVEF) ≥50%;
• Baseline oxygen saturation \>92%.
• Able to take oral medication and without gastrointestinal disorders that would significantly affect drug absorption.
• Considered by the investigator to be able to safely receive sonrotoclax initiation and dose ramp-up.
• Participants of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for the protocol-specified period after the last dose of study treatment.

You may not qualify if:

• Disease already transformed to acute myeloid leukemia (AML).
• Prior treatment with chemotherapy, sonrotoclax, or other BCL-2 inhibitors.
• Uncontrolled active infection, including severe bacterial, fungal, or viral infection.
• Active hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection, or active tuberculosis that is not adequately controlled.
• Significant uncontrolled cardiac, hepatic, renal, or other major organ dysfunction that, in the investigator's judgment, would preclude safe study treatment.
• Active graft-versus-host disease (GVHD) after prior allogeneic hematopoietic stem cell transplantation or ongoing requirement for systemic immunosuppressive therapy.
• Anticipated need for continuous use of a strong CYP3A inhibitor during sonrotoclax initiation and dose ramp-up that cannot be discontinued or replaced.
• Uncontrolled high risk of tumor lysis syndrome (TLS) that, in the investigator's judgment, makes the participant unsuitable for sonrotoclax treatment.
• Pregnant or breastfeeding women.
• Known severe hypersensitivity to sonrotoclax, azacitidine, or any of their excipients.
• Concurrent participation in another interventional clinical study without meeting applicable discontinuation requirements.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead
• BeiGene: collaborator

Study Sites (6)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

RECRUITING

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Shanghai Jiading District Central Hospital

Shanghai, China

NOT YET RECRUITING

Shanghai Minhang District Central Hospital

Shanghai, China

NOT YET RECRUITING

Shanghai Qingpu District Central Hospital

Shanghai, China

NOT YET RECRUITING

Xinhua Hospital, Shanghai Jiao Tong University

Shanghai, China

NOT YET RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Xianmin Song, MD

CONTACT

+86 13501672508; shongxm@sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Department of Hematology

Study Record Dates

• First Submitted: October 4, 2026
• First Posted: October 21, 2026
• Study Start: October 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)