CM336 Plus Daratumumab and Lenalidomide in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

NCT07830485 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate whether CM336, a BCMA/CD3 bispecific antibody, in combination with daratumumab and lenalidomide can induce deep and durable responses in adults with transplant-ineligible newly diagnosed multiple myeloma (NDMM). The study will also evaluate the safety of this treatment combination. The main questions it aims to answer are:

• How many participants achieve minimal residual disease (MRD) negativity after 6 treatment cycles?
• What side effects occur during treatment with CM336 combined with daratumumab and lenalidomide?
• How many participants respond to treatment and how deep are these responses?
• How long does MRD negativity and treatment response last?
• How long do participants remain free from disease progression? All participants will receive the study treatment. There is no comparison group in this study. Participants will:
• Receive CM336 by subcutaneous injection together with subcutaneous daratumumab and oral lenalidomide in 28-day treatment cycles.
• Undergo regular blood tests, bone marrow examinations, MRD assessments, and disease assessments to monitor treatment response and safety.
• Be monitored throughout the study for treatment-related adverse events.

Conditions

Multiple Myeloma

Keywords

Transplant-ineligible multiple myeloma; BCMA/CD3 bispecific antibody; CM336; Newly diagnosed multiple myeloma; Minimal residual disease

Outcome Measures

Primary Outcomes (1)

• Minimal residual disease (MRD) negative rate

  Proportion of participants achieving minimal residual disease (MRD) negativity after 6 treatment cycles.

  After 6 treatment cycles (each cycle is 28 days)

Secondary Outcomes (7)

• Incidence and severity of adverse events (AEs)

  From the first dose of CM336 through 30 days after the last dose of CM336, up to approximately 18 months.

• Duration of MRD negativity

  From the first documented MRD-negative assessment until disease progression, death, or end of follow-up, assessed up to approximately 36 months

• Overall Response Rate (ORR)

  Up to 18 treatment cycles (each cycle is 28 days)

• Very Good Partial Response or Better Rate (≥VGPR)

  Up to 18 treatment cycles (each cycle is 28 days)

• Complete Response Rate (CRR)

  Up to 18 treatment cycles (each cycle is 28 days)

Study Arms (1)

CM336 plus Dara-R

EXPERIMENTAL

Enrolled participants will receive up to 18 cycles of treatment with CM336 in combination with daratumumab and lenalidomide. Each treatment cycle is 28 days.

Drug: CM336 (BCMA/CD3 bispecific antibody); Drug: Daratumumab; Drug: Lenalidomide

Interventions

CM336 (BCMA/CD3 bispecific antibody) DRUG

CM336 is administered subcutaneously (SC) using a step-up dosing regimen of 3 mg on Day 1, 20 mg on Day 4, 80 mg on Day 7, and 160 mg on Day 10. The first administration of the target dose is considered Cycle 1 Day 1 of the target-dose phase. During Cycle 1, CM336 160 mg is administered once weekly. From Cycle 2 through Cycle 18, CM336 160 mg is administered every 4 weeks.

CM336 plus Dara-R

Daratumumab DRUG

Daratumumab is administered subcutaneously at a dose of 1800 mg in 28-day treatment cycles. One dose is administered on Day 0 before initiation of the CM336 step-up dosing regimen. During the CM336 target-dose treatment phase, daratumumab is administered once weekly during Cycles 1-2, every 2 weeks during Cycles 3-6, and every 4 weeks during Cycles 7-18.

CM336 plus Dara-R

Lenalidomide DRUG

Lenalidomide is administered orally at 25 mg once daily on Days 1-21 of each 28-day treatment cycle during Cycles 1-18. The starting dose may be adjusted for participants with renal impairment, frailty, or advanced age based on creatinine clearance and investigator judgment.

CM336 plus Dara-R

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign a written informed consent form (ICF).
• Age 18 to 75 years.
• Newly diagnosed symptomatic multiple myeloma according to International Myeloma Working Group (IMWG) criteria. Patients who have received no more than one cycle of anti-myeloma therapy before enrollment are eligible.
• Not planned to undergo autologous stem cell transplantation as first-line treatment and meeting at least one of the following criteria, including but not limited to:
• Age ≥65 years;
• Eastern Cooperative Oncology Group (ECOG) performance status of 3-4;
• Considered unable to tolerate autologous stem cell transplantation based on investigator assessment.
• Measurable disease, defined by at least one of the following:
• Serum M-protein ≥10 g/L by serum protein electrophoresis (SPEP); for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead;
• Urine M-protein ≥200 mg/24 hours;
• If neither serum nor urine M-protein meets the above criteria, involved serum free light chain (FLC) ≥100 mg/L with an abnormal serum FLC ratio (normal range: 0.26-1.65).
• Adequate hepatic function, defined as:
• Total bilirubin \<1.5 × upper limit of normal (ULN), except for participants with Gilbert syndrome, who must have total bilirubin \<3 × ULN;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
• Adequate renal function, defined as creatinine clearance ≥30 mL/min calculated using the Cockcroft-Gault formula.

You may not qualify if:

• Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or primary or secondary plasma cell leukemia.
• Central nervous system (CNS) involvement or clinical evidence of leptomeningeal involvement.
• Known intolerance, hypersensitivity, allergy, or contraindication to daratumumab, lenalidomide, or CM336.
• Severe and/or uncontrolled cardiovascular disease, including:
• Unstable angina;
• Symptomatic congestive heart failure;
• Myocardial infarction within 6 months prior to enrollment;
• Severe and uncontrolled cardiac arrhythmias;
• Any other cardiovascular or cerebrovascular condition deemed by the investigator to make participation inappropriate.
• Active infection, including:
• Human immunodeficiency virus (HIV) infection;
• Active hepatitis B infection (HBV DNA positive);
• Active hepatitis C infection (HCV RNA positive);
• Active or latent syphilis infection (Treponema pallidum antibody positive);
• Active pulmonary tuberculosis, as evidenced by chest imaging or other relevant examinations within 3 months before screening or during the screening period;

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, Tianjin Municipality, 300000, China

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

daratumumab; Lenalidomide

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Gang An

CONTACT

+86 13502181109; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): April 15, 2029
• Study Completion (Estimated): April 30, 2031
• Last Updated: September 21, 2026

Record last verified: 2026-09

Locations

CN (1)