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Plasma Cell Myeloma RefractoryPhase 1/2NCT04643002

Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

A Phase 1/2 study testing Isatuximab, Dexamethasone and Pomalidomide in people with Plasma Cell Myeloma Refractory, run by Sanofi at 25 sites in 9 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Plasma Cell Myeloma Refractory
What is being tested?
Isatuximab, Dexamethasone and Pomalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
258 participants
Where
25 sitesin 9 countries
Study dates
25 Jan 2021to 20 Apr 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

25 sites in 9 countries. Contact the study team or a site near you to ask about taking part.

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

800-633-1610 ext. option 6

contact-us@sanofi.com

25 sites in 9 countries

United States5 sites, 4 recruiting

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

    Ann Arbor, Michigan, 48109

    Recruiting

  • Winship Cancer Institute of Emory University- Site Number : 8400010

    Atlanta, Georgia, 30322

    Recruiting

  • Roswell Park Cancer Institute- Site Number : 8400008

    Buffalo, New York, 14263

    Recruiting

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

    Chicago, Illinois, 60612

    Completed

  • The Ohio State University- Site Number : 8400012

    Columbus, Ohio, 43210

    Recruiting

Other trials in United States

France4 sites, 4 recruiting

  • Investigational Site Number : 2500002

    Lille, 59037

    Recruiting

  • Investigational Site Number : 2500001

    Nantes, 44093

    Recruiting

  • Investigational Site Number : 2500003

    Paris, 75013

    Recruiting

  • Investigational Site Number : 2500004

    Paris, 75015

    Recruiting

Other trials in France

South Korea4 sites, 4 recruiting

  • Investigational Site Number : 4100001

    Seoul, Seoul-teukbyeolsi, 03080

    Recruiting

  • Investigational Site Number : 4100004

    Seoul, Seoul-teukbyeolsi, 03722

    Recruiting

  • Investigational Site Number : 4100002

    Seoul, Seoul-teukbyeolsi, 06351

    Recruiting

  • Investigational Site Number : 4100003

    Seoul, Seoul-teukbyeolsi, 06591

    Recruiting

Other trials in South Korea

Australia3 sites, 3 recruiting

  • Investigational Site Number : 0360002

    Melbourne, Victoria, 3065

    Recruiting

  • Investigational Site Number : 0360001

    Richmond, Victoria, 3121

    Recruiting

  • Investigational Site Number : 0360006

    Wollongong, New South Wales, 2500

    Recruiting

Other trials in Australia

Israel3 sites, 3 recruiting

  • Investigational Site Number : 3760002

    Jerusalem, 9112001

    Recruiting

  • Investigational Site Number : 3760003

    Ramat Gan, 5262100

    Recruiting

  • Investigational Site Number : 3760001

    Tel Aviv, 6423906

    Recruiting

Other trials in Israel

Germany2 sites, 2 recruiting

  • Investigational Site Number : 2760006

    Frankfurt, 60590

    Recruiting

  • Investigational Site Number : 2760008

    Lübeck, 23562

    Recruiting

Other trials in Germany

Greece2 sites, 2 recruiting

  • Investigational Site Number : 3000002

    Athens, 106 76

    Recruiting

  • Investigational Site Number : 3000001

    Athens, 115 28

    Recruiting

Other trials in Greece

Italy1 site, 1 recruiting

  • Investigational Site Number : 3800001

    Meldola, Reggio Emilia, 47014

    Recruiting

Other trials in Italy

Norway1 site, 1 recruiting

  • Investigational Site Number : 5780001

    Oslo, 0450

    Recruiting

Other trials in Norway

About this study

Official title: Phase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol

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.

Read the 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.

Being tested
Isatuximab, Dexamethasone, Pomalidomide, Belantamab mafodotin, Pegenzileukin
Keywords
anti-CD38 monoclonal antibody, master protocol, combination therapy, CD38 resistance, interleukin 2, ROCK2 inhibitor, anti-CD47 agent

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IsatuximabDrug

    Also called SAR650984, Sarclisa®

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

  • DexamethasoneDrug

    Pharmaceutical form: Tablet; Route of administration: Oral

  • PomalidomideDrug

    Also called Pomalyst®

    Pharmaceutical form: Capsule; Route of administration: Oral

  • Belantamab mafodotinDrug

    Also called BLENREP®

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

  • PegenzileukinDrug

    Also called SAR444245

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

  • SAR439459Drug

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

  • BelumosudilDrug

    Also called SAR445761,, Rezurock

    Pharmaceutical form: tablet; route of administration: oral

  • EvorpaceptDrug

    Also called ALX148

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

Study groups in NCT04643002
Study groupRoleWhat they receive
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.
Receives: Drug: Isatuximab; Drug: Dexamethasone; Drug: Pomalidomide
isatuximab + SAR439459 + dexamethasone (Substudy 02)ExperimentalSAR439459 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).
Receives: Drug: Isatuximab; Drug: Dexamethasone; Drug: SAR439459
isatuximab + dexamethasone + belantamab mafodotin (Substudy 03)ExperimentalBelantamab 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.
Receives: Drug: Isatuximab; Drug: Dexamethasone; Drug: Belantamab mafodotin
Isatuximab + pegenzileukin (Substudy 04)ExperimentalPegenzileukin 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.
Receives: Drug: Isatuximab; Drug: Pegenzileukin
Experimental: Isatuximab + Dexamethasone + Belumosudil (Substudy 05)ExperimentalIsatuximab 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
Receives: Drug: Isatuximab; Drug: Dexamethasone; Drug: Belumosudil
Isatuximab + evorpacept + dexamethasone (Substudy 06)ExperimentalIsatuximab 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
Receives: Drug: Isatuximab; Drug: Dexamethasone; Drug: Evorpacept

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

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

  3. 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.

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

Secondary outcomes (28)

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

    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.

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

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

    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.

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

  3. Part 1 (dose finding, experimental substudies): VGPR 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.

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

  4. Part 2 (expansion, independent experimental substudies): VGPR 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.

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

  5. Clinical benefit rate (CBR) in each treatment arm

    CBR, defined as the proportion of participants with sCR, CR, VGPR, PR, or minimal response, according to the 2016 IMWG criteria assessed by Investigator based on central laboratory values and local imaging.

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

  6. Duration of Response (DOR) in each treatment arm

    DOR, defined as the time from the date of the first response that is subsequently confirmed for patients achieving PR or better to the date of first documented PD or death, whichever happens first.

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

  7. Time to First Response (TT1R) in each treatment arm

    TT1R, defined as the time from the date of first treatment to the date of first response (PR or better) that is subsequently confirmed.

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

  8. Time to Best Response (TTBR) in each treatment arm

    TTBR, defined as the time from the date of first treatment to the date of first occurrence of best overall response (PR or better) that is subsequently confirmed.

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

  9. Number of participants with treatment emergent adverse events and serious adverse events in each treatment arm

    Safety and tolerability assessed in terms of adverse events/SAEs, including second primary malignancies, laboratory parameters, vital signs, and findings from physical examination.

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

  10. Progression-free survival (PFS) in each treatment arm

    PFS is defined as the time from the date of first treatment to disease progression based on the Investigator assessment according to 2016 IMWG criteria or death from any cause, whichever happens first.

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

  11. Overall Survival (OS) in each treatment arm

    OS is defined as the time from the date of first treatment to death from any cause.

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

  12. Immunogenicity of isatuximab and novel agents

    Incidence of anti-drug antibodies (ADAs) for novel agents (experimental arms) and isatuximab.

    Measured: Multiple timepoints up to approximately 28 months after the First patient in or scheduled assessment

  13. Concentration of novel agents (experimental arms) and isatuximab (Ctrough)

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  14. Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)

    The EORTC QLQ-C30 will be used to assess cancer-specific HRQL, disease and treatment-related symptoms and impact of symptoms. This endpoint will be assessed for Part 1 (dose optimization, independent and controlled experimental substudies) and Part 2 (expansion, independent and controlled experimental substudies).

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.

  15. Disease- and treatment-related quality of life will be assessed using the EORTC multiple myeloma module (QLQ-MY20) questionnaire

    The EORTC QLQ-MY20 will be used to measure myeloma-specific HRQL, disease and treatment-related symptoms and impact of symptoms. This endpoint will be assessed for Part 1 (dose optimization, independent and controlled experimental substudies) and Part 2 (expansion, independent and controlled experimental substudies).

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.

  16. Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)

    A single item from the FACT-G GP5 will be used to assess the global impact of side effects. This endpoint will be assessed for Part 1 (dose optimization, independent and controlled experimental substudies) and Part 2 (expansion, independent and controlled experimental substudies).

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.

  17. Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales

    Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales will be utilized as anchors to estimate/confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores. This endpoint will be assessed for Part 1 (dose optimization, independent and controlled experimental substudies) and Part 2 (expansion, independent and controlled experimental substudies).

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.

  18. The intensity of skeletal-related events (SRE)- related bone pain will be assessed using the skeletal-related bone pain numeric rating scale (SRE-BP-NRS) for control and experimental arms -Substudy 02

    The SRE-BP-NRS) will be used to assess the intensity of SRE-related bone pain (on average and at its worst) for control arm only

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at end of treatment and at first follow-up visit. The cycle is 28 days.

  19. SRE Incidence for control and experimental arms- Substudy 02

    SRE incidence, defined as the proportion of participants who experienced pathological fracture, radiation to bone, spinal cord compression, or surgery to bone as a first bone event.

    Measured: Continuous throughout study assessment (up to approximately 28 months)

  20. Time to First Occurrence of SRE Assessment for control and experimental arms (Substudy 02)

    Time to first occurrence of SRE is defined as time from the date of randomization to the occurrence of first SRE.

    Measured: Continuous throughout study assessment (up to approximately 28 months)

  21. Assessment of Health care resource utilization related with SREs for control and experimental arms -Substudy 02

    The Health Care Resource Use-SREs questionnaire (HCRU-SREs) will be used to assess the use of health care resources associated with these events.

    Measured: On Day1 Cycle 1, then every 2 cycles for the first year; then every 3 cycles thereafter, at End of treatment and at first follow-up visit. The cycle is 28 days.

  22. To assess patient-reported visual functioning for experimental arm only -Substudy 03

    An NEI VFQ-25 will be used to assess patient-reported visual functioning.

    Measured: On Day1 Cycle 1, End of treatment and at first follow-up visit. The cycle is 28 days.

  23. Maximum concentration observed after the first infusion (Cmax) for Belumosudil - Substudy 05

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  24. Time to reach Cmax (tmax) for Belumosudil - Substudy 05

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  25. Area under the concentration versus time curve calculated using the trapezoidal method from 0 to 8h (AUC0-8h) for Belumosudil - Substudy 05

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  26. Maximum concentration observed after the first infusion (Cmax) for Evorpacept - Substudy 06

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  27. Time to reach Cmax (tmax) for Evorpacept - Substudy 06

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

  28. Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval for evorpacept (AUC0-t)- Substudy 06

    Measured: Multiple timepoints during Cycle 1. The cycle is 28 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2020
  2. Study start25 Jan 2021
  3. Primary completion13 Sep 2027 (estimated)
  4. Study completion20 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
258 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04643002
Sponsor's protocol ID
ACT16482
Other IDs
U1111-1244-2598, 2024-514988-25, 2020-003024-16
Status last verified
Oct 2026
First submitted
20 Oct 2020
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Isatuximab, Dexamethasone and Pomalidomide in people with Plasma Cell Myeloma Refractory, run by Sanofi at 25 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, France, South Korea, Australia, Israel and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Trial Transparency email recommended (Toll free number for US & Canada) (800-633-1610 ext. option 6, contact-us@sanofi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04643002.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.

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