Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This study is a first-in-human, Phase 1, open-label study that will evaluate safety and anti-myeloma activity of ISB 2001 in participants with relapsed/refractory multiple myeloma (R/R MM).

Detailed Description
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The study will enroll participants with R/R MM that have been treated with immunomodulatory drugs (IMiDs), proteasome inhibitors, and anti-CD38 therapies either in combination or as a single agent and are refractory to, or intolerant of, established therapies known to provide clinical benefit in MM. The study will be conducted in two phases: Part 1: Dose escalation phase Part 2: Dose expansion phase Dose escalation will continue until either the maximum tolerated dose (MTD) is defined, the maximum planned dose is reached, or a recommended phase 2 dose (RP2D) is selected. Dose expansion cohorts will be initiated to further confirm safety and optimal biologically active dose at each putative recommended Phase 2 dose(s). Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment, or participant withdrawal from the study.

Official Title
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A Phase 1, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 2001 in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: ISB 2001
* Drug: ISB 2001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with pathologically confirmed MM with measurable M-protein: serum and/or 24 hour urine, serum-free light chains or measurable isolated plasmacytoma Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less Must have adequate hematologic, hepatic, renal, and cardiac functions Exclusion Criteria: Active malignant central nervous system involvement Uncontrolled infection requiring systemic antibiotic therapy or other serious infection prior to C1D1 History of autoimmune disease requiring systemic immunosuppressive therapy Any concurrent or uncontrolled medical, comorbid, psychiatric or social condition that would limit compliance with study procedures, interfere with the study results, substantially increase the risk of AEs, compromise ability to provide written informed consent or, in the opinion of the Investigator, constitute a hazard for participating in this study. Female subjects who are lactating and breastfeeding or have a positive pregnancy test during the screening period or on Day 1 before first dose of ISB 2001.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants with R/R MM will be administered ISB 2001 weekly on Days 1, 8, 15, and 22 of each 28-day cycle, with an additional step-up dose in Cycle 1 on Day 4. Treatment cycle duration is 28 days. Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment or participant withdrawal from the study | Drug: ISB 2001<br>* Participants will receive escalating doses of ISB 2001<br>|
| Experimental: Part 2: Dose Expansion<br>Dose expansion cohorts will be initiated to further confirm safety and optimal biologically active dose at each putative recommended Phase 2 dose(s). Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment or participant withdrawal from the study. | Drug: ISB 2001<br>* Participants will receive injection of ISB 2001 at 2 putative recommended Phase 2 doses as determined in Part 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs) |  | Up to 18 months | 
| Number of Dose-Limiting Toxicities (DLT) During the First 28 Days After the First Administration of ISB 2001 (Cycle 1) in Each Cohort (Part 1) |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of ISB 2001 in Serum |  | Up to 28 days | 
| Time to Reach Maximum Concentration (Tmax) of ISB 2001 in Serum |  | Up to 28 days | 
| Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB 2001 in Serum |  | Up to 28 days | 
| Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 2001 in Serum |  | Up to 28 days | 
| Percent Incidence of Anti-Drug Antibody (ADA), Neutralizing Antibody (nAb) and Titer of ADA From Baseline Until End-of-Treatment (EOT) |  | Baseline to 18 months | 
| Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG) |  | 18 months | 
| Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG) |  | 18 months | 
| Duration of Response (DOR) Based on International Myeloma Working Group (IMWG) |  | 18 months | 
| Time to Progression (TTP) |  | 18 months | 
| Time to Next Treatment (TTNT) |  | 18 months | 
| Time to Response (TTR) |  | 18 months | 
| Progression Free Survival (PFS) |  | 18 months | 
| Overall Survival (OS) |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ISB 2001, Relapsed/refractory multiple myeloma, Open-label, Dose escalation, Dose expansion