Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
mRNA-2736, First-in-human, FIH, Dose-escalation
Brief summary
This study is designed to evaluate the safety and tolerability of mRNA-2736 in participants with RRMM.
Detailed description
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.
Interventions
BIOLOGICALmRNA-2736
mRNA-2736 will be administered IV.
Sponsors
ModernaTX, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Experiencing Adverse Events | Up to 1 year |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Maximum Plasma Concentration (Cmax) | 0 (predose) to 96 hours postdose |
| Duration of Response (DOR) | Up to 2 years |
| Progression-free Survival (PFS) | Up to 2 years |
| Overall Survival (OS) | Up to 3 years |
| Clinical Benefit Rate (CBR) | Up to 2 years |
Countries
Canada, United States
Outcome results
None listed