mRNA-2736 for Participants With Relapsed or Refractory Multiple Myeloma (RRMM)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and tolerability of mRNA-2736 in participants with RRMM.

Detailed Description
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This open-label, Phase 1, dose-escalation, first-in-human (FIH) clinical study of mRNA-2736 in participants with RRMM is designed to evaluate the safety and tolerability of escalating doses of mRNA-2736, administered intravenously (IV), to determine maximum tolerated dose and/or recommended Phase 2 dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mRNA-2736.

Official Title
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A Phase 1, Open-Label, Multicenter, Study of mRNA-2736 in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: mRNA-2736


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: RRMM with prior exposure to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-cluster of differentiation (CD38) monoclonal antibody. Participants must have received at least 3 prior lines of therapy or be triple-class refractory. Participants that are intolerant of a proteasome inhibitor, IMiD, or aCD38 are eligible. Measurable disease defined as at least 1 of the following: Serum M-protein ≥0.5 grams/deciliter Urine M-protein ≥200 milligrams (mg)/24 hour Involved free light chain (FLC) ≥100 mg/liter and an abnormal FLC ratio Plasmacytoma with a single diameter ≥2 centimeters Bone marrow plasma cells >30% Key Exclusion Criteria: Known central nervous system (CNS) myeloma or clinical signs and symptoms of CNS involvement of myeloma. Active plasma cell leukemia, defined as peripheral blood plasma cells ≥20%. History of plasma cell leukemia is allowed. Radiotherapy or cytotoxic chemotherapy within 2 weeks prior to Day 1 (Baseline), except palliative radiotherapy of limited field is permissible within 2 weeks after discussion with the Sponsor medical monitor. Antibody-based immunotherapy (monoclonal antibody, bispecific antibody, antibody drug conjugate, radioimmunoconjugate) within 21 days prior to Day 1 (Baseline). Proteasome inhibitor therapy within 14 days prior to Day 1 (Baseline). Immunomodulatory agent therapy within 7 days of Day 1 (Baseline). Autologous hematopoietic cell transplant within 100 days prior to Day 1 (Baseline). Allogeneic hematopoietic cell transplant within 180 days prior to Day 1 (Baseline). Participants should have no evidence or ongoing treatment for acute or chronic graft versus host disease. Genetically modified adoptive cellular therapy (for example, chimeric antigen receptor T cell, chimeric antigen receptor natural killer) within 12 weeks prior to Day 1 (Baseline). Corticosteroid therapy ≥140 mg prednisone or equivalent cumulative dose within 14 days prior to Day 1 (Baseline). Active hepatitis B or C, or laboratory evidence for a chronic infection with hepatitis B or C at the time of screening. Participants with a past or resolved hepatitis B infection (presence of hepatitis B core antibody and absence of hepatitis B surface antigen) are eligible. Participants positive for hepatitis C virus (HCV) antibody are eligible only if negative for HCV RNA. Note: Other inclusion and exclusion criteria may apply.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-2736<br>Participants will receive mRNA-2736. | Biological: mRNA-2736<br>* mRNA-2736 will be administered IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Adverse Events |  | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) |  | 0 (predose) to 96 hours postdose | 
| Area Under the Concentration-time Curve (AUC) |  | 0 (predose) to 96 hours postdose | 
| Maximum Effect/Concentration of the Expressed Protein (Emax) |  | 0 (predose) to 96 hours postdose | 
| Area Under the Effect Concentration (AUEC) |  | 0 (predose) to 96 hours postdose | 
| Overall Response Rate (ORR) |  | Up to 2 years | 
| Clinical Benefit Rate (CBR) |  | Up to 2 years | 
| Duration of Response (DOR) |  | Up to 2 years | 
| Progression-free Survival (PFS) |  | Up to 2 years | 
| Overall Survival (OS) |  | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-2736, First-in-human, FIH, Dose-escalation