Isatuximab in Combination With Novel Agents in RRMM - Master Protocol
NCT ID: NCT04643002
Last Updated: 2025-08-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
258 participants
INTERVENTIONAL
2021-01-25
2028-04-20
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01)
* Isatuximab, intravenous (IV) doseweekly (QW) × 4 weeks (Cycle 1), followed by every two weeks (Q2W) (subsequent cycles).
* Pomalidomide dose by mouth daily Day 1 to Day 21.
* Dexamethasone dose by mouth QW.
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
Pomalidomide
Pharmaceutical form: Capsule; Route of administration: Oral
isatuximab + SAR439459 + dexamethasone (Substudy 02)
SAR439459 in combination with isatuximab and dexamethasone
Part 1:
2 dose levels (DLs) of IV SAR439459:
* DL1 SAR439459 dose Q2W.
* DL2 SAR439459 dose Q2W.
* Isatuximab dose IV QW × 5 weeks (Cycle 1), followed by Q2W administrations (subsequent cycles).
* Dexamethasone fixed dose and schedule: QW by mouth In Cycle 1, the first administration of SAR439459 (Day 1) will precede isatuximab by 1 week (first dose of isatuximab will be at Cycle 1 Day 8).
Part 2:
* SAR439459 IV dose Q2W.
* Isatuximab IV dose QW × 5 weeks (Cycle 1), followed by Q2W administrations (subsequent cycles).
* Dexamethasone fixed dose and schedule: QW by mouth. In Cycle 1, the first administration of SAR439459 (Day 1) will precede isatuximab by 1 week (first dose of isatuximab will be at Cycle 1 Day 8).
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
SAR439459
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)
Belantamab mafodotin in combination with isatuximab and dexamethasone
Part 1:
1 DL of IV belantamab mafodotin in Part 1 and de-escalation dose DL-1:
* DL1 belantamab mafodotin IV dose QW4 or de-escalation dose DL-1 QW8
* Isatuximab dose, IV QW × 4 weeks (Cycle 1), followed by Q2W (subsequent cycles).
* Dexamethasone fixed dose and schedule: QW by mouth.
Part 2:
* Isatuximab IV dose QW × 4 weeks (Cycle 1), followed by Q2W (subsequent cycles).
* Belantamab mafodotin IV dose Q4W or Q8W
* Dexamethasone fixed dose and schedule: QW by mouth.
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
Belantamab mafodotin
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Isatuximab + pegenzileukin (Substudy 04)
Pegenzileukin in combination with isatuximab
Part 1- dose escalation:
* Up to 3 DLs of IV pegenzileukin are planned to be evaluated:
* DL1 will explore pegenzileukin at Q2W.
* DL2 will explore pegenzileukin at Q2W.
* DL3 will explore pegenzileukin at Q2W.
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles).
Part 1 - dose optimization:
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles).
* Pegenzileukin at potential doses (DL A and DL B) Q2W.
Part 2 (dose expansion):
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles).
* Pegenzileukin IV dose Q2W.
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Pegenzileukin
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)
Isatuximab in combination with belumosudil and dexamethasone Part 1- dose escalation: During the first cycle, belumosudil will be evaluated in monotherapy during 2 to 4 weeks, then isatuximab and dexamethasone will be added, and continued for the subsequent cycles.
* Belumosudil by mouth at Dose Level (DL) 1, DL2, DL3, and DL4
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth
Part 1- dose optimization:
* Belumosudil at potential doses (DL A and DL B), daily by mouth
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth
Part 2- dose expansion:
* Belumosudil dose daily, by mouth
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
Belumosudil
Pharmaceutical form: tablet; route of administration: oral
Isatuximab + evorpacept + dexamethasone (Substudy 06)
Isatuximab in combination with evorpacept and dexamethasone
Part 1- dose escalation:
* Evorpacept IV dose Q2W
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth Part 1- dose optimization
* Evorpacept IV at potential doses (DL A and DL B), Q2W
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth
Part 2- dose expansion:
* Evorpacept IV dose Q2W
* Isatuximab IV dose QW × 4 weeks, followed by Q2W (subsequent cycles)
* Dexamethasone fixed dose and schedule: QW by mouth
Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
Evorpacept
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Interventions
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Isatuximab
Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
Pomalidomide
Pharmaceutical form: Capsule; Route of administration: Oral
Belantamab mafodotin
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pegenzileukin
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
SAR439459
Pharmaceutical form: Solution for injection; Route of administration: Intravenous
Belumosudil
Pharmaceutical form: tablet; route of administration: oral
Evorpacept
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
ALL
No
Sponsors
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Sanofi
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Sciences & Operations
Role: STUDY_DIRECTOR
Sanofi
Locations
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Winship Cancer Institute, Emory University- Site Number : 8400010
Atlanta, Georgia, United States
University of Illinois-Chicago - College of Medicine- Site Number : 8400007
Chicago, Illinois, United States
University of Michigan Health System - Ann Arbor- Site Number : 8400004
Ann Arbor, Michigan, United States
Roswell Park Cancer Institute- Site Number : 8400008
Buffalo, New York, United States
Investigational Site Number : 0360006
Wollongong, New South Wales, Australia
Investigational Site Number : 0360002
Melbourne, Victoria, Australia
Investigational Site Number : 0360001
Richmond, Victoria, Australia
Investigational Site Number : 2500002
Lille, , France
Investigational Site Number : 2500001
Nantes, , France
Investigational Site Number : 2500004
Paris, , France
Investigational Site Number : 2500003
Paris, , France
Investigational Site Number : 2760006
Frankfurt, , Germany
Investigational Site Number : 2760008
Lübeck, , Germany
Investigational Site Number : 3000002
Athens, , Greece
Investigational Site Number : 3000001
Athens, , Greece
Investigational Site Number : 3760002
Jerusalem, , Israel
Investigational Site Number : 3760003
Ramat Gan, , Israel
Investigational Site Number : 3760001
Tel Aviv, , Israel
Investigational Site Number : 3800001
Meldola, Reggio Emilia, Italy
Investigational Site Number : 5780001
Oslo, , Norway
Investigational Site Number : 6200001
Coimbra, , Portugal
Investigational Site Number : 6200002
Porto, , Portugal
Puerto Rico Medical Research Center- Site Number : 8400005
HATO REY, Puerto Rico, Puerto Rico
Investigational Site Number : 4100004
Seoul, Seoul-teukbyeolsi, South Korea
Investigational Site Number : 4100002
Seoul, Seoul-teukbyeolsi, South Korea
Investigational Site Number : 4100003
Seoul, Seoul-teukbyeolsi, South Korea
Investigational Site Number : 4100001
Seoul, Seoul-teukbyeolsi, South Korea
Countries
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Central Contacts
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Trial Transparency email recommended (Toll free number for US & Canada)
Role: CONTACT
Facility Contacts
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Other Identifiers
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U1111-1244-2598
Identifier Type: REGISTRY
Identifier Source: secondary_id
2024-514988-25
Identifier Type: REGISTRY
Identifier Source: secondary_id
2020-003024-16
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
ACT16482
Identifier Type: -
Identifier Source: org_study_id
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