A Study of CM336 in Patients With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a multi-center, open-label, Phase 1/2 study in China to evaluate the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of CM336 in patients with relapsed or refractory multiple myeloma. This study consists of a dose escalation part (Phase 1) and a dose extension part (Phase 2 ). The safety and tolerability of CM336 will be evaluated in Phase 1 study, as well as the maximum tolerated dose (MTD) and the recommended dose level for Phase 2 study will be determined. The efficacy of CM336 will be evaluated in Phase 2 study.

Official Title
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A Multi-center, Open-label, Phase 1/2 Clinical Study of CM336 Injection in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: CM336_group 1
* Drug: CM336_group 2a
* Drug: CM336_group 2b
* Drug: CM336_group 3a
* Drug: CM336_group 3b
* Drug: CM336_group 4a
* Drug: CM336_group 4b
* Drug: CM336_group 5
* Drug: CM336_group 6a
* Drug: CM336_group 6b
* Drug: CM336_group 7
* Drug: CM336_group 8a
* Drug: CM336_group 8b
* Drug: CM336_group 9
* Drug: CM336_RP2D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group Performance Status (ECOG) of 0-1. Patients with relapsed or refractory MM who have failed or are intolerant to all therapies with known clinical benefit; patients must have received at least 2 prior anti-myeloma therapies which must contain at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD), and one anti-CD38 monoclonal antibody (if available). Exclusion Criteria: Patients who had received BCMA-targeted therapy. Patients who had received CAR-T therapy. Patients who had received anti-tumor therapy within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of CM336.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1, Dose escalation<br>There are 14 dose groups in dose escalation part ( Phase 1 study). | Drug: CM336_group 1<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 0.04mg of CM336 on the first day of first cycle (C1D1), 0.04mg on C1D8, 0.04mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 2a<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 0.04mg of CM336 on the first day of first cycle (C1D1), 0.2mg on C1D8, 1.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 2b<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 0.2mg of CM336 on the first day of first cycle (C1D1), 0.2mg on C1D8, 0.2mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 3a<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 0.2mg of CM336 on the first day of first cycle (C1D1), 1.0mg on C1D8, 5.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 3b<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 1.0mg of CM336 on the first day of first cycle (C1D1), 1.0mg on C1D8, 1.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 4a<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 1.0mg of CM336 on the first day of first cycle (C1D1), 5.0mg on C1D8, 15.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 4b<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 2.0mg of CM336 on the first day of first cycle (C1D1), 2.0mg on C1D8, 2.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 5<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 2.0mg of CM336 on the first day of first cycle (C1D1), 8.0mg on C1D8, 24.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 6a<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 2.0mg of CM336 on the first day of first cycle (C1D1), 10.0mg on C1D8, 40.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 6b<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 3.0mg of CM336 on the first day of first cycle (C1D1), 3.0mg on C1D8, 3.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 7<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 3.0mg of CM336 on the first day of first cycle (C1D1), 15.0mg on C1D8, 60.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 8a<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 3.0mg of CM336 on the first day of first cycle (C1D1), 15.0mg on C1D8, 75.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 8b<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 4.0mg of CM336 on the first day of first cycle (C1D1), 4.0mg on C1D8, 4.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>Drug: CM336_group 9<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Patients will take 4.0mg of CM336 on the first day of first cycle (C1D1), 20.0mg on C1D8, 90.0mg on C1D15 and subsequent treatment cycles until there is evidence of disease progression, unacceptable toxicity or other reasons for treatment discontinuation.<br>|
| Experimental: Phase 2, Dose expansion<br>Based on the data of phase 1, the dose level recommended for the phase 2 study (RP2D) will be evaluated. | Drug: CM336_RP2D<br>* CM336 will be administered subcutaneously (SC) once a week (QW). Individual subjects may continue study treatment until disease progression/relapse, unacceptable toxicity, withdrawal of consent, receipt of other anti-MM therapies, death, loss to follow-up, or the end of study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLTs) | Dose-limiting toxicities (DLTs) | 21 days after the first dose | 
| Adverse events (AEs) | Adverse events (AEs), including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Up to 4.5 years | 
| Overall Response Rate (ORR) | Assessed according to International Myeloma Working Group (IMWG) response criteria. | up to 4.5 years |