Sonrotoclax and BCMA Bispecific Antibody in Newly Diagnosed Systemic AL Amyloidosis Based on t(11;14) Genetic Stratification

NCT07687004 | Not Yet Recruiting Phase 1

• 1 other identifier: IIT2026059
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, single-center, phase Ib/II clinical trial designed to evaluate the tolerability of sonrotoclax plus dexamethasone in this phase Ib/II umbrella study and to determine the recommended phase II dose (RP2D). It also aims to assess the safety and hematologic response rate of sonrotoclax plus dexamethasone in patients with newly diagnosed systemic light-chain amyloidosis (NDAL) harboring t(11;14), and of a BCMA/CD3 bispecific antibody in patients with NDAL without t(11;14). In addition, this study seeks to explore a chemotherapy-free treatment strategy based on t(11;14)-guided genetic stratification.

Conditions

Multiple Myeloma (MM)

Keywords

BCMA/CD3 bispecific antibody; Sonrotoclax; t(11;14)

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

  DLTs will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and will include most grade 3 or higher events, as defined in the protocol.

  Up to 28 days

• Phase 1b and 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events Leading to Discontinuation, and Adverse Events of Special Interest (AESIs).

  Up to 30 days after the last dose of the study drug

• Phase 2: Rate of Hematologic Very Good Partial Response (VGPR) or Better

  Proportion of participants achieving a hematologic response of VGPR or better (≥VGPR) of anti-BCMA/CD3 bispecific antibody (CM336), assessed using consensus criteria for AL amyloidosis hematologic response.

  6 months

Secondary Outcomes (8)

• Time to First Hematologic Response (TTR)

  From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.

• Best Hematologic Response Achieved

  From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months.

• Duration of Hematologic Response (DOR)

  From the date of first documented hematologic response to the date of disease progression or death, whichever occurs first, up to approximately 24 months.

• Overall Response Rate (ORR)

  The overall response rate (ORR) was evaluated at the end of cycle 4, 6, and 12 (28 days per cycle).

• Progression-Free Survival (PFS)

  From the first dose to progression from any cause, up to approximately 36 months.

Study Arms (3)

Phase 2: CM336

EXPERIMENTAL

Subcutaneous CM336 administration, step-up dosing, Dose and frequency of CM336 according to the protocol.

Drug: CM336 (BCMA/CD3 bispecific antibody)

Phase 1b Dose Escalation: Sonrotoclax

EXPERIMENTAL

Dose-escalation and de-escalation to determine the maximum tolerated dose (MTD) of sonrotoclax plus dexamethasone.

Drug: Sonrotoclax

Phase 2: Sonrotoclax

EXPERIMENTAL

Patients assigned to the sonrotoclax cohort will receive sonrotoclax in combination with dexamethasone. Sonrotoclax will be administered orally once daily (QD) at the recommended phase II dose (RP2D) determined during the phase Ib dose-finding stage.

Drug: Sonrotoclax

Interventions

Sonrotoclax DRUG

Administered orally daily

Also known as: BGB-11417

Phase 1b Dose Escalation: Sonrotoclax; Phase 2: Sonrotoclax

CM336 (BCMA/CD3 bispecific antibody) DRUG

CM336 is a bispecific T-cell engager targeting B-cell maturation antigen (BCMA) and CD3. In this study, CM336 is administered subcutaneously with a step-up dosing strategy in Cycle 1 (3 mg Day 1, 20 mg Day 4, 40 mg Day 8 and onwards weekly).

Phase 2: CM336

Eligibility Criteria

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

You may qualify if:

• Able to understand and voluntarily sign the informed consent form (ICF).
• Age ≥18 years and ≤70 years.
• Confirmed diagnosis of primary light-chain amyloidosis, according to the diagnostic and treatment guidelines for primary light-chain amyloidosis, 2021 revised edition.
• Subjects entering the phase Ib dose-escalation stage must also have confirmed t(11;14) translocation by FISH or other genetic testing.
• Newly diagnosed systemic AL amyloidosis, with no prior systemic anti-tumor therapy for AL amyloidosis.
• Measurable disease at screening, defined as:
• a) Difference between involved and uninvolved serum free light chains (dFLC) \>20 mg/L.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤3.
• Adequate hepatic function, defined as total bilirubin \<1.5 × upper limit of normal (ULN) (total bilirubin \<3 × ULN for patients with Gilbert syndrome), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 × ULN.
• Adequate renal function, defined as creatinine clearance ≥30 mL/min, calculated using the Cockcroft-Gault formula.
• Baseline oxygen saturation \>92% on room air.
• Hematologic parameters within 7 days before the start of screening meeting the following criteria: absolute neutrophil count ≥1.0 × 10⁹/L, hemoglobin ≥70 g/L without whole blood or red blood cell transfusion within 7 days, and platelet count ≥70 × 10⁹/L without whole blood transfusion, platelet transfusion, or thrombopoietin receptor agonist treatment within 7 days; or deemed suitable for enrollment by the investigator based on clinical judgment.
• Women of non-childbearing potential are eligible. Female patients of childbearing potential must have a negative serum β-human chorionic gonadotropin or urine pregnancy test at screening.
• Male patients, women of childbearing potential, and their partners must voluntarily use effective contraceptive measures, as judged by the investigator, during the treatment period.
• Male patients must agree not to donate sperm from the initial screening period until 90 days after the last dose of study treatment.

You may not qualify if:

• Non-AL amyloidosis, including hereditary amyloidosis and other non-AL types of amyloidosis.
• Diagnosis of symptomatic multiple myeloma, according to the Chinese Guidelines for the Diagnosis and Treatment of Multiple Myeloma, 2022 revised edition. Patients whose diagnosis is based solely on a serum free light-chain ratio ≥100 are not excluded.
• Peripheral neuropathy \> grade 2 or painful neuropathy ≥ grade 2 at screening, regardless of whether the patient is currently receiving medication.
• History of another malignancy, other than AL amyloidosis, within 5 years before randomization.
• Known intolerance, allergy, or contraindication to the active ingredients of the BCMA/CD3 bispecific antibody or sonrotoclax.
• Unstable or active cardiovascular or cerebrovascular disease, meeting any of the following criteria:
• Unstable angina, symptomatic myocardial ischemia, myocardial infarction, or coronary revascularization within 180 days before the first dose;
• NT-proBNP \>8500 ng/L;
• Congestive heart failure with hospitalization for cardiovascular disease within 4 weeks before randomization;
• Heart failure judged by the investigator to be caused by ischemic heart disease, such as prior myocardial infarction with elevated cardiac enzymes and electrocardiographic changes, or uncorrected valvular disease, rather than AL amyloid cardiomyopathy;
• History of sustained ventricular tachycardia or ventricular fibrillation, or history of atrioventricular (AV) node or sinoatrial (SA) node dysfunction requiring a pacemaker or implantable cardioverter-defibrillator (ICD) but without implantation. Patients with an implanted pacemaker or ICD may be enrolled;
• Corrected QT interval using Fridericia's formula (QTcF) \>500 msec. Patients with an implanted pacemaker may be enrolled regardless of the corrected QT interval result;
• Supine systolic blood pressure \<90 mmHg;
• Any other cardiovascular or cerebrovascular disease that, in the investigator's judgment, makes the subject unsuitable for participation in this study.
• Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 300020, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Gang An, MD, PhD

CONTACT

13502181109; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 7, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 7, 2026

Record last verified: 2026-05

Locations

CN (1)