CM336-SOC for Dynamically High-Risk Multiple Myeloma Study

A Prospective, Single-Arm, Single-Center, Phase II Clinical Study of CM336 Combined With SOC Therapy in Patients With Dynamically High-Risk Multiple Myeloma

This is a single-arm, open-label study to evaluate the efficacy and safety of CM336 combined with SOC therapy in patients with dynamically high-risk multiple myeloma.

Inclusion Criteria:

1. Able to understand and voluntarily sign the informed consent form (ICF).
2. Aged ≥18 and ≤75 years.
3. Has measurable disease, meeting at least one of the following criteria: serum M-protein ≥5 g/L as measured by serum protein electrophoresis (SPEP); or, for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead; or 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 in the presence of an abnormal serum FLC ratio (normal FLC ratio: 0.26 to 1.65).
4. Has received only one prior line of standard anti-myeloma therapy: standard induction therapy comprising at least two of the following: a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody; followed by autologous hematopoietic stem cell transplantation or consolidation therapy, and standard maintenance therapy.
5. Meets the definition of functional high-risk multiple myeloma according to the EMN consensus: disease progression or relapse within 18 months after initiation of any first-line therapy.
6. Liver function tests meet the following criteria: total bilirubin <1.5 × upper limit of normal (ULN) (except that patients with Gilbert's syndrome must have total bilirubin <3 × ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
7. Renal function tests meet the following criterion: creatinine clearance ≥30 mL/min, calculated using the Cockcroft-Gault formula.
8. Complete blood count within 7 days before screening meets the following criteria: white blood cell (WBC) count ≥1.5 × 10⁹/L, absolute neutrophil count ≥1.0 × 10⁹/L, hemoglobin ≥70 g/L, and platelet count ≥75 × 10⁹/L if bone marrow plasma cells are <50%, or platelet count ≥50 × 10⁹/L if bone marrow plasma cells are ≥50%; or, in the investigator's judgment based on the actual clinical situation, the subject is considered suitable for enrollment.
9. For patients receiving hematopoietic growth factor support, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and platelet agonists, etc. (e.g., eltrombopag, TPO, interleukin-11), there must be an interval of 2 weeks between growth factor support and screening assessment.
10. For patients receiving blood product transfusions: there must be an interval of at least 2 weeks between the screening hemoglobin assessment and the last red blood cell (RBC) transfusion, and an interval of at least 1 week between the screening platelet assessment and the last platelet transfusion.
11. The subject is able to receive the prophylactic anticoagulation recommended in the study.
12. Female subjects of childbearing potential must meet both of the following conditions: agree to use effective contraception from the date of signing the informed consent form, during treatment with the study drug, and for 3 months after the last dose of the study drug; and have a negative serum pregnancy test result at screening.

Exclusion Criteria:

1. Primary plasma cell leukemia or secondary plasma cell leukemia.

2. Concurrent amyloidosis.

3. Concurrent central nervous system (CNS) involvement.

4. Prior treatment with BCMA-targeted therapy or CAR-T cell therapy.

5. Known intolerance, allergy, or contraindication to glucocorticoids or BCMA/CD3 bispecific antibody products.

6. Clinically significant cardiac disease, including: myocardial infarction before randomization; or unstable or uncontrolled disease related to or affecting cardiac function, such as unstable angina, congestive heart failure, or New York Heart Association class III-IV cardiac function. Uncontrolled arrhythmia or clinically significant ECG abnormalities. Baseline corrected QT interval (QTc) >470 msec on 12-lead ECG at screening.

7. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.

8. Active hepatitis B or C infection. Hepatitis serology testing is required at screening. If hepatitis B surface antigen or hepatitis B core antibody is positive, a negative DNA polymerase chain reaction (PCR) result must be confirmed before enrollment; for patients receiving anti-hepatitis B antiviral therapy, a negative DNA PCR result must be confirmed before enrollment. If hepatitis C antibody is positive, RNA PCR testing must be performed, and a negative result must be confirmed before enrollment.

9. Pregnant or breastfeeding women.

10. Life expectancy <6 months.

11. Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect absorption of the study treatment.

12. Major surgery within 2 weeks before the start of randomization, such as surgery requiring general anesthesia; incomplete recovery from surgery; or planned surgery during the study period. Kyphoplasty or vertebroplasty is not considered major surgery.

    Note: Subjects scheduled to undergo surgical procedures under local anesthesia may participate in the study.

13. Receipt of a live attenuated vaccine within 4 weeks before the first dose of study drug.