Recruiting
Phase 1
Phase 2

Isatuximab & Novel Agents

Sponsor:

Sanofi

Code:

NCT04643002

Conditions

Plasma Cell Myeloma Refractory

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Isatuximab

Dexamethasone

Pomalidomide

Belantamab mafodotin

Pegenzileukin

Study Details

Brief 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.

Conditions

Plasma Cell Myeloma Refractory

Study ID

NCT04643002

Start date

Jan 25, 2021

Status verified date

Jun, 2026

Completion date

Apr 20, 2028

Anticipated

Primary completion date

Sep 13, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

258 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 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.

experimental: 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).

experimental: 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.

experimental: 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.

experimental: 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

experimental: 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

Interventions

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

Primary outcome measure

  • Part 1 (dose finding, experimental substudies): Determination of recommended dose of novel agents in combination with isatuximab [ Time Frame: Through the end of cycle 1 (approximately 6 weeks) ]
  • Part 2 (expansion, controlled experimental substudies): VGPR Rate (Rate of Very Good Partial Response Rate or Better) [ Time Frame: Up to approximately 28 months after the First patient in or scheduled assessment ]
  • Part 2 (expansion, independent experimental substudies): Overall Response Rate (ORR) in independent experimental substudies [ Time Frame: Up to approximately 28 months after the First patient in or scheduled assessment ]

Central Contacts and Locations

Central contacts

Trial Transparency email recommended (Toll free number for US & Canada)

800-633-1610contact-us@sanofi.com

Locations

Winship Cancer Institute of Emory University- Site Number : 8400010

Recruiting

Atlanta, Georgia, United States, 30322

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

Recruiting

Ann Arbor, Michigan, United States, 48109

Roswell Park Cancer Institute- Site Number : 8400008

Recruiting

Buffalo, New York, United States, 14263

The Ohio State University- Site Number : 8400012

Recruiting

Columbus, Ohio, United States, 43210

More Information

Sponsor

Sanofi

Last update posted

Jun 16, 2026

Last verified

Jun, 2026

Keywords

  • anti-CD38 monoclonal antibody
  • master protocol
  • combination therapy
  • CD38 resistance
  • interleukin 2
  • ROCK2 inhibitor
  • anti-CD47 agent

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sanofi on 2026-06-16.