Clinical trial NCT05918250: mRNA-2736 for Participants With Relapsed or Refractory Multiple Myeloma (RRMM)
Official title: A Phase 1, Open-Label, Multicenter, Study of mRNA-2736 in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: mRNA-2736
First-in-human
FIH
Dose-escalation
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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 exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: Up to 1 year
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 0 (predose) to 96 hours postdose
measure: Area Under the Concentration-time Curve (AUC)
timeFrame: 0 (predose) to 96 hours postdose
measure: Maximum Effect/Concentration of the Expressed Protein (Emax)
timeFrame: 0 (predose) to 96 hours postdose
measure: Area Under the Effect Concentration (AUEC)
timeFrame: 0 (predose) to 96 hours postdose
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Hospital
state: Alabama
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: UW Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
Study officials:
References: