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

Ichnos Sciences SA20 sites in 2 countries81 target enrollmentOctober 25, 2017

ConditionsRelapsed/Refractory Multiple Myeloma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Relapsed/Refractory Multiple Myeloma
Sponsor: Ichnos Sciences SA
Enrollment: 81
Locations: 20
Primary Endpoint: Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 25, 2017

End Date

December 15, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Ichnos Sciences SA

Responsible Party

Sponsor

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

Outcomes

Primary Outcomes

Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1)

Time Frame: 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)

Time Frame: 28 days

Secondary Outcomes

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.)