Phase II Study of Sonrotoclax Combined With Chemotherapy in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Risk-stratified Treatment of Sonrotoclax Combined With Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: a Multicenter, Phase II Study

This single-armed study aims to investigate the safety and efficacy of sonrotoclax in combination with intensive chemotherapy in subjects with newly diagnosed AML. Subjects will be stratified based on the genetic risk classification of 2022 European LeukemiaNet (ELN) recommendations and MRD status to receive specific consolidation therapy after the induction therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: sonrotoclax; Drug: idarubicin/daunorubicin; Drug: Cytarabine; Drug: Azacitidine; Procedure: allo-HSCT

Detailed Description

47 subjects who meet the eligibility criteria will receive no more than 2 cycles (each cycle is 28 days) of induction therapy with sonrotoclax on day5-14 combined with the standard 3+7 intensive chemotherapy regimen (3+7 regimen) containing cytarabine, and daunorubicin or idarubicin. In cycle(C)1 of induction therapy, sonrotoclax will be administered orally once daily by a 4-day dose rump-up of 20mg on Day(D)5, 40mg on D6, 80mg on D7, and 160mg on D8-14. The first 6 subjects will be enrolled in a Safety Run-in period in C1 to assess tolerability and determine the final sonrotoclax regimen. Within 42 days or before the next cycle of therapy, if ≤1 of 6 subjects has dose-limiting toxicities (DLT), the study will be continued with the sonrotoclax dose regimen as above, and if ≥2 of 6 subjects have DLTs, the dose will be adjusted. Adjustment may include reducing the dose, shortening the duration of each cycle, or terminating the study, based on the DLTs' characteristics.

Subjects who achieve a composite complete remission (CRc) after induction therapy will receive further consolidation therapy, which regimen will be decided based on the ELN risk at diagnosis and MRD status detected by MFC after induction therapy.

After consolidation, subjects will receive once daily sonrotoclax orally combined with azacitidine (AZA) subcutaneously once daily alternating with AZA monotherapy every 2 cycles as maintenance therapy until unacceptable toxicity, 12 months, recurrence, death, withdrawal of informed consent, or study termination determined by investigators.

This single-armed study aims to investigate the safety and efficacy of a risk-stratified regimen of sonrotoclax in combination with intensive chemotherapy in subjects with newly diagnosed AML.

• Study Type: Interventional
• Enrollment (Estimated): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed untreated acute myeloid leukemia patients;
2. Age range from 18 to 75 years old;
3. The Eastern Cooperative oncology Group (ECOG) score is ≤ 2 points;

4. The following organ functional conditions must be met:

   • Liver function (bilirubin<2mg/dL, AST and/or ALT<3 x ULN)
   • Renal function (blood creatinine clearance rate ≥ 30 mL/min)
   • Cardiac function (left ventricular ejection fraction ≥ 50%)

5. If the age is ≥ 60 years old, the following conditions must be further met;

   • Charlson comorbidity index (CCI) ≤ 1
   • Activity of Daily Living Scale (ADL)>100
   • No cognitive impairment, Mini Mental State Examination (MMSE) ≥ 28
   • No impairment of living ability, Short Physical Performance Battery Protocol (SPPB) ≥ 9
6. Women with fertility must have a negative serum pregnancy test ≤ 7 days before the first administration. In addition, they must use efficient contraceptive methods before the first dose of study medication, during the study treatment period, and for ≥ 180 days after the last dose of study medication.
7. Non infertile males must use efficient contraceptive methods during the study treatment period and within ≥ 90 days after the last dose of the study medication. During this period, they are not allowed to donate sperm.
8. The patient fully understands this study, obtains an informed consent form (ICF) signed by the patient or their legal representative, and follows the research protocol and follow-up process.
9. The expected lifespan is greater than 12 weeks.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL)；
2. Malignant tumor in the past 2 years, except for cured localized skin cancer, superficial bladder cancer, cervical cancer or cancer in situ of breast cancer, and localized prostate cancer with Gleason score ≤ 6;
3. Uncontrolled concurrent diseases, including but not limited to: ongoing or active uncontrolled infections, cardiovascular or mental illnesses/social situations that may limit compliance with research requirements;
4. It is known that the subjects are positive for hepatitis B or hepatitis C infection, except those whose viral load cannot be detected within 3 months (Note: patients with HBcAb+but HBsAg - can only meet the condition if hepatitis B virus (HBV) DNA cannot be detected in the detection with sensitivity ≤ 20 IU/mL. In this case, patients should receive regular monitoring of HBV DNA and receive prophylactic antiviral drug treatment according to the central diagnosis and treatment routine; Patients with HCV antibody+are eligible only if they cannot detect HCV RNA and are willing to monitor HCV reactivation；
5. Receive any moderate or strong CYP3A4 inhibitor (7 days or 5 half-lives, whichever is longer) or moderate or strong CYP3A4 inducer (14 days or 5 half-lives, whichever is longer) treatment before the first use of Sonrotoclax；
6. Patients who are known to have hypersensitivity reactions to any component in the study protocol;
7. Known central nervous system involvement in AML;
8. Previously received organ, bone marrow, or peripheral blood organ transplantation；
9. Participate in another therapeutic clinical study simultaneously；
10. Pregnant or lactating women, or male and female patients planning to have children during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Assigned Interventions; Experimental: Sonrotoclax combined with intensive chemotherapy. Subjects receive induction therapy consisting of sonrotoclax combined with a 3+7 regimen. According to the ELN risks and MRD status, subjects who achieve composite complete remission (CRc) proceed with consolidation therapy, and allogeneic hematopoietic stem-cell transplant (allo-HSCT) can be included per investigator's decision. After the consolidation, subjects will receive sonrotoclax combined with azacitidine (AZA) alternating with AZA monotherapy every 2 cycles as maintenance therapy until intolerable toxicity, 12 months, relapse, death, withdrawal of informed consent, or study termination determined by investigators, whichever occurs first.

Drug: sonrotoclax; Orally once daily, on D5-14. A 4-day dose ramp-up is required for the first induction. The dosing regimen will be determined in the Safety Run-in phase. If a second induction is needed, dose ramp-up is not required. In the consolidation therapy phase, subjects in the group with favorable risk and MRD negative do not need to receive Sonrotoclax treatment, and subjects in the group with favorable risk and MRD positive, or with intermediate and adverse risk will receive sonrotoclax on D1-7 at the target dose determined in the safety run-in phase, dose ramp-up is not required. In the maintenance therapy phase, subjects will receive once daily sonrotoclax on D1-14 at the target dose determined in the safety run-in phase.; Other Names: BGB11417; Drug: idarubicin/daunorubicin; idarubicin: On D1-3, intravenously, 10 mg/m^2 for subjects aged <60 years, 6 mg/m^2 for subjects aged ≥60 years daunorubicin: On D1-3, intravenously, 60 mg/m^2 for subjects aged <60 years, 40 mg/m^2 for subjects aged ≥60 years; Other Names: IDA/DNR; Drug: Cytarabine; In induction therapy phase: intravenously, 100 mg/m^2 on D1-7. In consolidation therapy phase: subjects with favorable-risk and MRD negative will receive cytarabine intravenously at 2 g/m^2/q12h for those aged <60 years, at 1g/m^2/q12h for those ≥60 years on D1-3 or 3+7 regimen, and subjects with favorable-risk and MRD positive or intermediate or adverse-risk will receive cytarabine intravenously at 1 g/m^2/d q12h on D1-3(in combination with sonrotoclax).; Other Names: Ara-c; Drug: Azacitidine; 75 mg/m^2, subcutaneously, once daily, on D1-7; Other Names: AZA; Procedure: allo-HSCT; Per standard of procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS	event free survival rate	2-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission rate	Complete remission/complete remission with partial hematological recovery/complete remission with incomplete hematological recovery	Up to cycle 2 (each cycle is 28 days)
The complete remission rate of MRD negative	The complete remission rate of MRD negative	Up to cycle 2 (each cycle is 28 days)
RFS	relapse free survival rate	Only for subjects who have achieved CR, CRh, or CRi; The time from the first attainment of eligible remission (CR, CRh, or CRi) after the start of treatment to the recording of disease recurrence or death, whichever occurs first. Up to 24 months
OS	overall survival rate	up to 24 months
AE, SAE	Adverse event，Serious adverse events	up to 24 months
Early mortality rate	Mortality within 30 days after first study medication and within 60 days after first study medication	Within 30 and 60 days after the first study medication

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD and long-term survival	Evaluate the correlation with EFS and OS by grouping different remission states of MRD at the end of induction therapy and consolidation therapy	up to 24 months
HSCT rate	HSCT rate and exploration of the association between HSCT and EFS and OS	up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Collaborators: Ruijin Hospital; BeiGene
• Investigators: Principal Investigator: Junmin Li, Ruijin Hospital

Publications and helpful links

General Publications

• Zhang Y, Wu M, Jin Z, Yang L, Huang X, Li W, Zhu H, Wang W, Chen Q, Liu L, Chen Z, Wang S, Li J. Risk-stratified treatment of sonrotoclax with chemotherapy in newly diagnosed acute myeloid leukemia: a study protocol. Future Oncol. 2025 Apr;21(8):953-958. doi: 10.1080/14796694.2025.2469487. Epub 2025 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Acute myeloid leukemia; Sonrotoclax; Risk-stratified
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Cytarabine; Azacitidine; Daunorubicin; Idarubicin
• Other Study ID Numbers: BGB-11417-2001-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No