Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Biological: ISB 1342
- 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
- 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
- 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
- Arm && Interventions
Group Intervention Description ISB 1342 ISB 1342 Part 1: Cohorts of multiple ISB 1342 dose levels; Part 2: One dose regimen until disease progression or other discontinuation criterion is met
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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)
Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Duke Clinical Research Institute
🇺🇸Durham, North Carolina, United States
Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
🇫🇷Lille, France
Hôpital Saint-Antoine
🇫🇷Paris, France
CHRU de Tours - Hôpital Bretonneau
🇫🇷Tours, Cedex, France
CHU de Poitiers
🇫🇷Poitiers, Cedex, France
Institut Universitaire du Cancer de Toulouse - Oncopole
🇫🇷Toulouse, Cedex, France
Mayo Clinic Cancer Center (MCCC) - Rochester
🇺🇸Rochester, Minnesota, United States
CHU de Nantes - Hôtel-Dieu
🇫🇷Nantes, Cedex, France
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
L'Institut Paoli - Calmettes
🇫🇷Marseille, France
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, Cedex, France
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Centre Hospitalier Lyon-Sud
🇫🇷Pierre Benite, Cedex, France
CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
🇫🇷Pessac, Cedex, France
CHU Hôpital Henri Mondor
🇫🇷Créteil, France