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

Phase 1
Completed
Conditions
Relapsed/Refractory Multiple Myeloma
Registration Number
NCT03309111
Lead Sponsor
Ichnos Sciences SA
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
81
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Efficacy of ISB 1342 (duration of response [DOR]) (Part 1 and Part 2)28 days
Efficacy of ISB 1342 (time to treatment failure [TTF]) (Part 2)28 days
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
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 (time to disease progression [TTP]) (Part 2)28 days
Efficacy of ISB 1342 (disease control rate [DCR]) (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
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
Immunogenicity of ISB 1342 by anti-drug antibody (ADA) formation (Part 1 and Part 2)28 days
Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2)28 days
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
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
Efficacy of ISB 1342 (progression free survival [PFS]) (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.

Trial Locations

Locations (20)

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center

🇺🇸

Baltimore, Maryland, United States

Mayo Clinic Cancer Center (MCCC) - Rochester

🇺🇸

Rochester, Minnesota, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Mount Sinai Beth Israel

🇺🇸

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

Duke Clinical Research Institute

🇺🇸

Durham, North Carolina, United States

Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

CHU de Nantes - Hôtel-Dieu

🇫🇷

Nantes, Cedex, France

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Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
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