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.
Brief Title
Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Relapsed/Refractory Multiple Myeloma
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03309111
Org Class
Industry
Org Full Name
Ichnos Sciences SA
Org Study Id
ISB 1342-101
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Measure
Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1)
Outcome Time Frame
28 days
Outcome Measure
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)
Outcome Time Frame
28 days
Secondary Ids
Secondary Id
2016-005253-20
Secondary Outcomes
Outcome Time Frame
up to 30 days post last dose
Outcome Measure
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)
Outcome Time Frame
28 days
Outcome Measure
Maximum serum concentration (Cmax) of ISB 1342 (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Time to reach maximum observed plasma concentration (Tmax) of ISB 1342 (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Area under the serum concentration time curve from zero to time t (AUC0-t) of ISB 1342 (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Area under the curve from time zero to end of dosing interval (AUC0-tau) of ISB 1342 (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Immunogenicity of ISB 1342 by anti-drug antibody (ADA) formation (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
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)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (duration of response [DOR]) (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (disease control rate [DCR]) (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (time to minimal residual disease [MRD] negative status) (Part 1 and Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (progression free survival [PFS]) (Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (time to treatment failure [TTF]) (Part 2)
Outcome Time Frame
28 days
Outcome Measure
Efficacy of ISB 1342 (time to disease progression [TTP]) (Part 2)
Outcome Time Frame
Time from first dose until death from any cause or end of study collection, whichever is later, assessed up to 60 months.
Outcome Measure
Efficacy of ISB 1342 (overall survival [OS]) (Part 2)
Outcome Time Frame
28 days
Outcome Measure
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)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nishi Shah
Investigator Email
nisshah@montefiore.org