CM336 Plus Isatuximab for Newly Diagnosed Multiple Myeloma With Severe Renal Impairment (CM336-RI)

A Prospective, Single-arm, Single-center, Phase II Study of BCMA/CD3 Bispecific Antibody Combined With CD38 Monoclonal Antibody in Newly Diagnosed Multiple Myeloma Patients With Severe Renal Impairment

This study is a single-center, single-arm, open-label, Phase II interventional clinical trial designed to evaluate the efficacy and safety of a CM336 and isatuximab regimen in patients with newly diagnosed multiple myeloma (NDMM) accompanied by severe renal impairment ([eGFR] < 30 mL/min). Enrolled subjects will receive three consecutive cycles of induction therapy with CM336 in combination with isatuximab.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma (MM); Multiple Myeloma Light Chain Induced Renal Insufficiency
• Intervention / Treatment: Drug: CM336 Plus Isatuximab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gang An, PhD & MD; Phone Number: +86 13502181109; Email: angang@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China, 300000
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
    • Contact: Gang An, PhD & MD; Phone Number: 0086 13502181109; Email: angang@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 to 80 years.
2. Newly diagnosed symptomatic multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) criteria. Patients who have received up to 1 cycle of prior anti-myeloma therapy, excluding immunotherapeutic agents, are allowed to enroll.

3. Presence of measurable disease at diagnosis, meeting at least one of the following criteria:

   A.Serum M-protein ≥ 1 g/dL (> 10 g/L) measured by serum protein electrophoresis (SPEP) (for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead); OR

   B.Urine M-protein ≥ 200 mg/24 hours; OR

   C.If both serum and urine M-protein do not meet the above criteria, an abnormal serum free light chain (FLC) ratio (normal FLC ratio: 0.26 to 1.65) with an involved serum FLC level ≥ 100 mg/L.

4. Accompanied by myeloma-related renal impairment (RI), defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min (calculated using the Modification of Diet in Renal Disease [MDRD] formula). The type of renal impairment must be restricted to cast nephropathy, which can be confirmed by renal biopsy or by the investigator's clinical judgment based on light chain proteinuria. If urine albumin accounts for more than 30% of the total urine protein, a renal biopsy is mandatory to confirm cast nephropathy.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.

6. Adequate major organ function, meeting the following criteria:

   A. Hematological function:

   1. Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L, and without receiving granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 7 days, or pegylated G-CSF within 14 days prior to testing;
   2. Hemoglobin ≥ 60 g/L, and without receiving whole blood or red blood cell transfusions within 7 days prior to testing;
   3. Platelet count ≥ 50 × 10^9/L, and without receiving whole blood, platelet transfusions, or thrombopoietin receptor agonists (TPO-RAs) within 7 days prior to testing.

   B. Hepatic function:

   Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 × ULN, and total bilirubin ≤ 2 × ULN (subjects with a history of Gilbert's syndrome are eligible if direct bilirubin ≤ 2.0 × ULN).

   C. Coagulation function:

7. International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
8. No active concomitant malignancies or malignancies with an expected survival of less than 12 months.
9. Willingness to participate in the study, good compliance, and ability to sign the informed consent form (ICF).

Exclusion Criteria:

1. Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis, or secondary plasma cell leukemia.
2. Central nervous system (CNS) involvement or clinical evidence of meningeal involvement.
3. Severe and/or uncontrolled cardiac diseases, including: unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months prior to enrollment, severe and uncontrolled arrhythmias; or other cardiovascular/cerebrovascular diseases deemed unsuitable for study participation by the investigator.
4. Presence of active infections, including: HIV positive; active Hepatitis B (HBV-DNA positive); active Hepatitis C (HCV-RNA positive); active or latent syphilis infection (Treponema pallidum antibody positive); active tuberculosis (active TB infection indicated by chest imaging or other relevant tests within the past 3 months or during the screening period); or other active infections deemed unsuitable for study participation by the investigator.
5. Patients with concurrent malignancies; or severe concomitant diseases that, in the investigator's judgment, would severely compromise patient safety or interfere with study completion.
6. Pregnant or lactating women.
7. History of severe allergic reactions (Grade ≥ 3) or hypersensitivity to any components of the study drugs.
8. Unable or unwilling to sign the informed consent form.
9. Any other conditions that, in the opinion of the investigator, make the patient unsuitable for enrollment.

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: CM336 plus Isatuximab; Enrolled patients will receive 3 cycles of induction therapy with CM336 in combination with isatuximab.	Drug: CM336 Plus Isatuximab; CM336: Administered subcutaneously (SC) via a step-up dosing regimen, which includes a step-up dosing phase and a target dosing phase. Upon reaching the target dose, it will be administered once weekly. Isatuximab: Administered intravenously (IV) at a dose of 10 mg/kg, given weekly during Cycle 1, and every two weeks during Cycles 2 and 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Renal Response Rate (Minor Response or better)	The Overall Renal Response Rate is defined as the percentage of participants who achieve a renal response of Minor Response or better (including Minor Response, Partial Response, and Complete Response) according to the International Myeloma Working Group (IMWG) criteria for renal impairment.	At the end of Cycle 3 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematological Overall Response Rate (ORR)	The percentage of participants who achieve a hematological response of Partial Response (PR) or better (including PR, Very Good Partial Response [VGPR], Complete Response [CR], and Stringent Complete Response [sCR]) according to the International Myeloma Working Group (IMWG) uniform response criteria.	From the first dose of CM336 through 30 days after the last dose of CM336
MRD Negativity Rate	The percentage of participants who achieve MRD negativity in the bone marrow. MRD negativity is defined by a threshold of 10^-5, assessed via Next-Generation Flow (NGF) cytometry in accordance with IMWG criteria.	At the end of Cycle 3 (each cycle is 28 days)
Kinetics of Serum Free Light Chain (sFLC) Reduction	The rate and time to achieve a specific percentage or absolute reduction in involved serum free light chain (sFLC) levels from baseline.	From the first dose of CM336 through 30 days after the last dose of CM336
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety will be assessed by monitoring the incidence, nature, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), graded according to NCI CTCAE v5.0 and ASTCT criteria. Dose interruptions, modifications, or discontinuations due to toxicity will also be recorded.	From the first dose of CM336 through 30 days after the last dose of CM336.
PFS	The time from the start of the study treatment to the date of first documented disease progression (according to IMWG criteria) or death from any cause, whichever occurs first.	From the first dose of CM336 up to the date of first documented disease progression or death, up to approximately 24 months.
OS	The time from the start of the study treatment to the date of death from any cause.	From the first dose of CM336 up to the date of death from any cause, up to approximately 24 months.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: May 10, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: BCMA/CD3 bispecific antibody; CM336; Multiple Myeloma With Severe Renal Impairment
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; isatuximab
• Other Study ID Numbers: IIT2026037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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