Isatuximab in Combination With Novel Agents in RRMM - Master Protocol

Conditions

• Plasma Cell Myeloma Refractory

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Isatuximab — DRUG
  Pharmaceutical form: Concentrated solution for intravenous infusion; Route of administration: Intravenous infusion
• Dexamethasone — DRUG
  Pharmaceutical form: Tablet; Route of administration: Oral
• Pomalidomide — DRUG
  Pharmaceutical form: Capsule; Route of administration: Oral
• Belantamab mafodotin — DRUG
  Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Pegenzileukin — DRUG
  Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• SAR439459 — DRUG
  Pharmaceutical form: Solution for injection; Route of administration: Intravenous
• Belumosudil — DRUG
  Pharmaceutical form: tablet; route of administration: oral
• Evorpacept — DRUG
  Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Study Details

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.

Key Dates

Start date

Jan 25, 2021

Status verified

Mar 2026

Primary completion

Sep 13, 2027

Completion

Apr 20, 2028

Study Design

Enrollment

258 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

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

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) ]

Central Contacts

• Trial Transparency email recommended (Toll free number for US & Canada)
  800-633-1610
  [email protected]

Locations (5)

Find similar trials in Atlanta, GA

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