About this trial

The purpose of this umbrella study is to evaluate isatuximab when combined with novel agents with or without dexamethasone in participants with relapsed or refractory myeloma. Substudy 01 is the control Substudy. Substudies 02, 03, and 06 are controlled experimental substudies. Substudies 04 and 05 are independent experimental substudies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant must be 18 years of age inclusive or older.

Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line).

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

Disqualifiers

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

Uncontrolled infection within 14 days prior to first study intervention administration.

Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., 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.

Trial design

Design model

Parallel

Treatments tested in this trial

Isatuximab
Drug
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Drug
Pharmaceutical form: Tablet; Route of administration: Oral
Pomalidomide
Drug
Pharmaceutical form: Capsule; Route of administration: Oral
Belantamab mafodotin
Drug
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pegenzileukin
Drug
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
SAR439459
Drug
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
Belumosudil
Drug
Pharmaceutical form: tablet; route of administration: oral
Evorpacept
Drug
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Treatment groups

258 Participants

are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01)Active comparator 3 interventions

Group B: isatuximab + SAR439459 + dexamethasone (Substudy 02)Experimental treatment 3 interventions

Group C: isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)Experimental treatment 3 interventions

Group D: Isatuximab + pegenzileukin (Substudy 04)Experimental treatment 2 interventions

Group E: Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)Experimental treatment 3 interventions

Group F: Isatuximab + evorpacept + dexamethasone (Substudy 06)Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Part 1 (dose finding, experimental substudies): Determination of recommended dose of novel agents in combination with isatuximab

Determination or confirmation of the dose will be based on: safety and tolerability in terms of TEAEs/SAEs, dose-limiting toxicity occurrence, and laboratory parameters available information on PK (if appropriate) and biomarkers.

Time frame

Through the end of cycle 1 (approximately 6 weeks)

2

Part 2 (expansion, controlled experimental substudies): VGPR Rate (Rate of Very Good Partial Response Rate or Better)

VGPR or better rate is defined as the percentage of participants with a VGPR or better as defined by the 2016 IMWG response criteria, assessed by Investigator based on central laboratory values and local imaging.

Time frame