Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma

Sponsor

Ichnos Sciences SA (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05862012

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Drug: ISB 2001 Drug: ISB 2001	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2027

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Dose Escalation 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 Participants will receive escalating doses of ISB 2001
Experimental: Part 2: Dose Expansion 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 Participants will receive injection of ISB 2001 at 2 putative recommended Phase 2 doses as determined in Part 1.

Arm

Intervention/Treatment

Experimental: Part 1: Dose Escalation

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

Participants will receive escalating doses of ISB 2001

Experimental: Part 2: Dose Expansion

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

Participants will receive injection of ISB 2001 at 2 putative recommended Phase 2 doses as determined in Part 1.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.