Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

NCT04643002 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: ACT16482U1111-1244-25982024-514988-252020-003024-16
• Study Type: interventional
• Target: 258
• Locations: 11 countries
• Sites: 28

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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)

  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.

  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

  ORR, defined as the proportion of participants with stringent complete response (sCR), complete response (CR), VGPR, or partial response (PR), according to the 2016 IMWG criteria assessed by Investigator based on central laboratory values and local imaging.

  Up to approximately 28 months after the First patient in or scheduled assessment

Secondary Outcomes (28)

• Part 1 (dose finding, experimental substudies): ORR

  Up to approximately 28 months after the First patient in or scheduled assessment

• Part 2 (expansion, controlled experimental substudies): ORR

  Up to approximately 28 months after the First patient in or scheduled assessment

• Part 1 (dose finding, experimental substudies): VGPR or better

  Up to approximately 28 months after the First patient in or scheduled assessment

• Part 2 (expansion, independent experimental substudies): VGPR or better

  Up to approximately 28 months after the First patient in or scheduled assessment

• Clinical benefit rate (CBR) in each treatment arm

  Up to approximately 28 months after the First patient in or scheduled assessment

Study Arms (6)

Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01)

ACTIVE COMPARATOR

* 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.

Drug: Isatuximab; Drug: Dexamethasone; Drug: Pomalidomide

isatuximab + SAR439459 + dexamethasone (Substudy 02)

EXPERIMENTAL

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).

Drug: Isatuximab; Drug: Dexamethasone; Drug: SAR439459

isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)

EXPERIMENTAL

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.

Drug: Isatuximab; Drug: Dexamethasone; Drug: Belantamab mafodotin

Isatuximab + pegenzileukin (Substudy 04)

EXPERIMENTAL

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.

Drug: Isatuximab; Drug: Pegenzileukin

Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)

EXPERIMENTAL

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

Drug: Isatuximab; Drug: Dexamethasone; Drug: Belumosudil

Isatuximab + evorpacept + dexamethasone (Substudy 06)

EXPERIMENTAL

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

Drug: Isatuximab; Drug: Dexamethasone; Drug: Evorpacept

Interventions

Isatuximab DRUG

Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion

Also known as: SAR650984, Sarclisa®

Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01); Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05); Isatuximab + evorpacept + dexamethasone (Substudy 06); Isatuximab + pegenzileukin (Substudy 04); isatuximab + SAR439459 + dexamethasone (Substudy 02); isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)

Dexamethasone DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01); Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05); Isatuximab + evorpacept + dexamethasone (Substudy 06); isatuximab + SAR439459 + dexamethasone (Substudy 02); isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)

Pomalidomide DRUG

Pharmaceutical form: Capsule; Route of administration: Oral

Also known as: Pomalyst®

Control Arm: isatuximab + pomalidomide + dexamethasone (Substudy 01)

Belantamab mafodotin DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: BLENREP®

isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)

Pegenzileukin DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: SAR444245

Isatuximab + pegenzileukin (Substudy 04)

SAR439459 DRUG

Pharmaceutical form: Solution for injection; Route of administration: Intravenous

isatuximab + SAR439459 + dexamethasone (Substudy 02)

Belumosudil DRUG

Pharmaceutical form: tablet; route of administration: oral

Also known as: SAR445761,, Rezurock

Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)

Evorpacept DRUG

Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Also known as: ALX148

Isatuximab + evorpacept + dexamethasone (Substudy 06)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (28)

Winship Cancer Institute of Emory University- Site Number : 8400010

Atlanta, Georgia, 30322, United States

RECRUITING

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

Chicago, Illinois, 60612, United States

COMPLETED

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

Ann Arbor, Michigan, 48109, United States

RECRUITING

Roswell Park Cancer Institute- Site Number : 8400008

Buffalo, New York, 14263, United States

RECRUITING

The Ohio State University- Site Number : 8400012

Columbus, Ohio, 43210, United States

RECRUITING

Investigational Site Number : 0360006

Wollongong, New South Wales, 2500, Australia

RECRUITING

Investigational Site Number : 0360002

Melbourne, Victoria, 3065, Australia

RECRUITING

Investigational Site Number : 0360001

Richmond, Victoria, 3121, Australia

RECRUITING

Investigational Site Number : 2500003

Paris, Washington, 75651, France

RECRUITING

Investigational Site Number : 2500002

Lille, 59037, France

RECRUITING

Investigational Site Number : 2500001

Nantes, 44093, France

RECRUITING

Investigational Site Number : 2500004

Paris, 75015, France

RECRUITING

Investigational Site Number : 2760006

Frankfurt, 60590, Germany

RECRUITING

Investigational Site Number : 2760008

Lübeck, 23538, Germany

RECRUITING

Investigational Site Number : 3000002

Athens, 106 76, Greece

RECRUITING

Investigational Site Number : 3000001

Athens, 115 28, Greece

RECRUITING

Investigational Site Number : 3760002

Jerusalem, 9112001, Israel

RECRUITING

Investigational Site Number : 3760003

Ramat Gan, 5262100, Israel

RECRUITING

Investigational Site Number : 3760001

Tel Aviv, 6423906, Israel

RECRUITING

Investigational Site Number : 3800001

Meldola, Reggio Emilia, 47014, Italy

RECRUITING

Investigational Site Number : 5780001

Oslo, 0450, Norway

RECRUITING

Investigational Site Number : 6200001

Coimbra, 3000-075, Portugal

RECRUITING

Investigational Site Number : 6200002

Porto, 4434-502, Portugal

RECRUITING

Puerto Rico Medical Research Center- Site Number : 8400005

Hato Rey, Puerto Rico, 00917, Puerto Rico

RECRUITING

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

RECRUITING

Investigational Site Number : 4100004

Seoul, Seoul-teukbyeolsi, 03722, South Korea

RECRUITING

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 06351, South Korea

RECRUITING

Investigational Site Number : 4100003

Seoul, Seoul-teukbyeolsi, 06591, South Korea

RECRUITING

Related Links

• ACT16482 Plain Language Results Summary

MeSH Terms

Interventions

isatuximab; Dexamethasone; pomalidomide; belantamab mafodotin; belumosudil; ALX148

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 24, 2020
• Study Start: January 25, 2021
• Primary Completion (Estimated): September 13, 2027
• Study Completion (Estimated): April 20, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (5); DE (2); IT (1); GR (2); PT (2); PR (1); FR (4); NO (1); AU (3); IL (3); KR (4)