Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to assess safety, efficacy, pharmacokinetic (PK)/pharmacodynamic (PD), and immunogenicity with ISB 1342 in subjects with relapsed/refractory multiple myeloma.

Detailed Description
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This study is an open-label, multi-center, Phase 1 study of ISB 1342 in subjects with relapsed/refractory multiple myeloma refractory to proteasome inhibitors (PIs), immunomodulators (IMiDs), and daratumumab. There will be a dose escalation phase (Part 1) and dose expansion phase (Part 2). In Part 1 of the study, subjects will be treated at escalating dose levels. Once the recommended part 2 dose (RP2D) of ISB 1342 is declared in Part 1, the expansion phase (Part 2) will be initiated at the RP2D.

Official Title
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A Phase 1, First-in-Human, Multicenter, Open-Label, Two-Part Dose-Escalation and Cohort Expansion Study of Single-Agent ISB 1342 in Subjects With Previously Treated Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: ISB 1342


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of multiple myeloma with measurable disease (serum, urine, or free light chain) per International Myeloma Working Group (IMWG) criteria, including non-secretory or oligo-secretory multiple myeloma which has relapsed after or is refractory to prior therapies, including proteasome inhibitors (PIs), immunomodulators (IMiDs) and anti-CD38 targeted therapies (daratumumab, isatuximab). Eastern Cooperative Oncology Group (ECOG) performance-status score of 2 or less and 1 or less (for France). Adequate hematologic, renal, and hepatic functions Seronegative for hepatitis B antigen; positive hepatitis B tests can be further evaluated by confirmatory tests, and if viral load is negative, the subject can be enrolled. Seronegative for hepatitis C antibody; if positive, then further test for the presence of antigen by hepatitis C virus polymerase chain reaction (HCV PCR). If HCV antigen tests are negative, then the subject can be enrolled. Oxygen saturation level ≥92% on room air. Left ventricular ejection fraction (LVEF) ≥50% and no pericardial or pleural effusion at Screening Exclusion Criteria: Active central nervous system involvement Exposure to daratumumab or isatuximab within 2 months prior to the start of study treatment Active plasma cell leukemia Active infectious disease Clinically significant cardiovascular and respiratory conditions History of HIV infection Subjects requiring prohibited concomitant medications

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ISB 1342<br>Part 1: Cohorts of multiple ISB 1342 dose levels; Part 2: One dose regimen until disease progression or other discontinuation criterion is met | Biological: ISB 1342<br>* ISB-1342 is CD38 x CD3 BEAT® 1.0 bispecific antibody. ISB 1342 is administered by intravenous (IV) infusion or subcutaneous injection (SC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1) |  | 28 days | 
| Proportion of subjects with an investigator-assessed objective response (at least a partial response or better), complete response, disease control (stable disease or better) to ISB 1342, per International Myeloma Working Group (IMWG) criteria (Part 2) |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events based on frequency and severity as assessed by common terminology criteria for adverse events (CTCAE) v5.0 (Part 1 and Part 2) |  | up to 30 days post last dose | 
| Maximum serum concentration (Cmax) of ISB 1342 (Part 1 and Part 2) |  | 28 days | 
| Time to reach maximum observed plasma concentration (Tmax) of ISB 1342 (Part 1 and Part 2) |  | 28 days | 
| Area under the serum concentration time curve from zero to time t (AUC0-t) of ISB 1342 (Part 1 and Part 2) |  | 28 days | 
| Area under the curve from time zero to end of dosing interval (AUC0-tau) of ISB 1342 (Part 1 and Part 2) |  | 28 days | 
| Immunogenicity of ISB 1342 by anti-drug antibody (ADA) formation (Part 1 and Part 2) |  | 28 days | 
| Percent incidence of neutralizing antibody formation from positive anti-drug antibody (ADA) samples assessed from baseline until end of treatment (EOT) (Part 1 and Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (duration of response [DOR]) (Part 1 and Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (disease control rate [DCR]) (Part 1 and Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (time to minimal residual disease [MRD] negative status) (Part 1 and Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (progression free survival [PFS]) (Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (time to treatment failure [TTF]) (Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (time to disease progression [TTP]) (Part 2) |  | 28 days | 
| Efficacy of ISB 1342 (overall survival [OS]) (Part 2) |  | Time from first dose until death from any cause or end of study collection, whichever is later, assessed up to 60 months. | 
| Proportion of subjects with investigator-assessed objective response (at least a partial response or better), complete response, disease control (stable disease or better) to ISB 1342, per International Myeloma Working Group (IMWG) criteria (Part 1) |  | 28 days |