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NCT04643002PHASE1, PHASE2Recruiting

Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

Sanofi

Start Date

1/25/2021

Completion Date

4/20/2028

Summary

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.

Detailed Description

Participants will continue study treatment until disease progression, death, unacceptable toxicity, participant request to stop treatment, Investigator decision, or study termination by the Sponsor i.e., up to Aapproximately 28 months.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * 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). * 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, 06: Anti-CD38 therapy naïve or prior exposure to such drugs with a wash out of at least 12 months after the last dose. "Exposure" is defined as at least 2 cycles of therapy. * Substudies 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. * Substudy 04: Anti-CD38 and anti-B cell maturation antigen (BCMA) therapy (if available) prior exposed participants with RRMM. For anti-CD38, "Exposure" is defined as at least 2 cycles of therapy. For anti-BCMA therapy if available, exposure is defined by at least 2 cycles of therapy. * Substudy 05: Participants with RRMM with at least 2 cycles of prior exposure to anti-CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory. 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 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. * Uncontrolled or active hepatitis B virus (HBV) infection. * Active hepatitis C virus (HCV) infection. * Any of the following within 3 months prior to first study intervention administration: 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 first study intervention administration. * Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone. * Participants with a contraindication to treatment. * Vaccination with a live vaccine 4 weeks before the start of the study. * Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted. * Hemoglobin \<8 g/dL. * Platelets \<50 × 10\^9/L. * Absolute neutrophil count \<1.0 × 10\^9/L. * Creatinine clearance \<30 mL/min/1.73m2. * 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. Substudy 04: * Central nervous system or leptomeningeal disease. * Medical history of seizure. * Participants currently receiving hepatically metabolized narrow therapeutic index drugs (eg, digoxin, warfarin) if cannot be closely monitored. * Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs), except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc). The following are not exclusionary: vitiligo, childhood asthma that has resolved, psoriasis that does not require systemic treatment. * Prior allogeneic hematopoietic stem cell transplant (allo-HSCT). Substudy 05: \- Participant unable to swallow tablets. Substudy 06: * History of active autoimmune disorders. * History of autoimmune hemolytic anemia or autoimmune. thrombocytopenia. * Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD. * Prior allogenic hematopoietic stem cell transplant (allo-HSCT). * Patient with chronic active EBV infection. * Patients with known history of HLH. * Hemoglobin \< 9 g/dL. * Prior therapy with any anti-CD47 or anti signal regulatory protein alpha agent. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Interventions

DRUG

Isatuximab

DRUG

Dexamethasone

DRUG

Pomalidomide

DRUG

Belantamab mafodotin

DRUG

Pegenzileukin

DRUG

SAR439459

DRUG

Belumosudil

DRUG

Evorpacept

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Conditions

Plasma Cell Myeloma Refractory

Locations

Winship Cancer Institute of Emory University- Site Number : 8400010

Atlanta, Georgia 30322

United States

University of Illinois-Chicago - College of Medicine- Site Number : 8400007

Chicago, Illinois 60612

United States

University of Michigan Health System - Ann Arbor- Site Number : 8400004

Ann Arbor, Michigan 48109

United States

Roswell Park Cancer Institute- Site Number : 8400008

Buffalo, New York 14263

United States

The Ohio State University- Site Number : 8400012

Columbus, Ohio 43210

United States

Investigational Site Number : 0360006

Wollongong, New South Wales 2500

Australia

Investigational Site Number : 0360002

Melbourne, Victoria 3065

Australia

Investigational Site Number : 0360001

Richmond, Victoria 3121

Australia

Investigational Site Number : 2500003

Paris, Washington 75013

France

Investigational Site Number : 2500002

Lille, 59037

France

Investigational Site Number : 2500001

Nantes, 44093

France

Investigational Site Number : 2500004

Paris, 75015

France

Investigational Site Number : 2760006

Frankfurt, 60590

Germany

Investigational Site Number : 2760008

Lübeck, 23562

Germany

Investigational Site Number : 3000002

Athens, 106 76

Greece

Investigational Site Number : 3000001

Athens, 115 28

Greece

Investigational Site Number : 3760002

Jerusalem, 9112001

Israel

Investigational Site Number : 3760003

Ramat Gan, 5262100

Israel

Investigational Site Number : 3760001

Tel Aviv, 6423906

Israel

Investigational Site Number : 3800001

Meldola, Reggio Emilia 47014

Italy

Investigational Site Number : 5780001

Oslo, 0450

Norway

Puerto Rico Medical Research Center- Site Number : 8400005

Hato Rey, Puerto Rico 00917

Puerto Rico

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi 03080

South Korea

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi 03722

South Korea

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi 06351

South Korea

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi 06591

South Korea