Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

• Status: Recruiting
• Trial end date: 2026-02-11
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

Part 1 (dose finding, experimental substudies):

• To determine or confirm the recommended dose of novel agents when combined with isatuximab with or without dexamethasone in participants with RRMM.

• Part 2 (expansion, experimental substudies):

• To demonstrate the clinical benefit of novel agents combined with isatuximab with or without dexamethasone in terms of rate of very good partial response (VGPR) or better.

Secondary Objectives:

• To assess the overall response rate (ORR) in each treatment arm.

• To assess the clinical benefit rate (CBR) in each treatment arm.

• To assess the duration of response (DOR) in each treatment arm.

• To assess the time to first response (TT1R) in each treatment arm.

• To assess the time to best response (TTBR) in each treatment arm.

• To assess safety and tolerability in each treatment arm.

• To assess progression free survival (PFS) in each treatment arm.

• To assess overall survival (OS) in each treatment arm.

• To evaluate the potential immunogenicity of isatuximab and novel agents when applicable.

• To characterize the PK of isatuximab and novel agents.

• To assess disease and treatment related symptoms, cancer and disease specific health-related quality of life, global impact of side effects and confirm/establish clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores.

-Substudy 1 (Control Arm):

• To assess clinical outcomes assessments (COAs).

• To assess the incidence of skeletal related events (SREs).

• To assess the time to first occurrence of SRE.

• To assess health care resource utilization related with SREs.

-Substudy 2:

• To assess pain intensity related to skeletal related events (SREs).

• To assess the incidence of SREs.

• To assess the time to first occurrence of SRE.

• To assess health care resource utilization related with SREs.

-Substudy 3:

• To assess patient-reported visual functioning

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Dexamethasone; Pomalidomide

Criteria

Inclusion criteria :

• Participant must be 18 years of age inclusive or older

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Participants with relapsed or refractory MM who have received at least 3 prior lines of therapy for MM, including PIs and IMiDs or at least 2 prior lines if at least one of these lines consisted of 2 or more multiagent regimens (eg, Induction regimen with autologous stem cell transplant followed by maintenance).

• RRMM with measurable disease:

• Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or

• Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or

• Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio <0.26 or >1.65).

• Men or woman or childbearing potential should agree to use contraception.

• Substudy 01, 02, 03: Anti-CD38 therapy naïve or prior exposure to such drugs without being refractory but with a wash out of at least 6 months after the last dose. "Refractory" is defined as progressing within 60 days of last dose of anti-CD38 targeting therapy.

Exclusion criteria:

• Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.

• Uncontrolled infection within 14 days prior to randomization.

• Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to randomization, eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction <40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).

• Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.

• Uncontrolled or active hepatitis B virus (HBV) infection.

• Active hepatitis C virus (HCV) infection.

• Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.

• Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before randomization.

• Any anti-MM drug treatment within 14 days before randomization, including dexamethasone.

• Participants with a contraindication to treatment.

• Vaccination with a live vaccine 4 weeks before the start of the study.

• Hemoglobin <8 g/dL.

• Platelets <50 × 109/L.

• Absolute neutrophil count <1.5 × 109/L.

• Creatinine clearance <30 mL/min.

• Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN.

• Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN.

• Patients with grade 3 or 4 hypercalcemia

Substudy 01:

-Malabsorption syndrome or any condition that can significantly impact the absorption of pomalidomide.

Substudy 02:

• History of resected/ablated basal or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix, or other local tumors, even if considered cured by local treatment.

• Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior to the first dose of SAR439459.

• Prothrombin time or INR >1.5 × upper limit of normal (ULN).

Substudy 03:

• Current corneal epithelial disease except mild punctate keratopathy

• Patients who have received prior therapy with belantamab mafodotin

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.