Relapsed/Refractory Multiple Myeloma
Conditions
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.
Interventions
BIOLOGICALISB 1342
ISB-1342 is CD38 x CD3 BEAT® 1.0 bispecific antibody. ISB 1342 is administered by intravenous (IV) infusion or subcutaneous injection (SC)
Sponsors
Glenmark Pharmaceuticals S.A.
Ichnos Sciences SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2) | 28 days |
| Maximum serum concentration (Cmax) of ISB 1342 (Part 1 and Part 2) | 28 days |
Countries
France, United States
Outcome results
None listed