Clinical trial NCT03309111: Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Ichnos Sciences SA
Sponsor class: INDUSTRY
Collaborators: name: Glenmark Pharmaceuticals S.A.
First posted: 2017-10-13
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1)
timeFrame: 28 days
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)
timeFrame: 28 days
Secondary outcomes:
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)
timeFrame: up to 30 days post last dose
measure: Maximum serum concentration (Cmax) of ISB 1342 (Part 1 and Part 2)
timeFrame: 28 days
measure: Time to reach maximum observed plasma concentration (Tmax) of ISB 1342 (Part 1 and Part 2)
timeFrame: 28 days
measure: Area under the serum concentration time curve from zero to time t (AUC0-t) of ISB 1342 (Part 1 and Part 2)
timeFrame: 28 days
measure: Area under the curve from time zero to end of dosing interval (AUC0-tau) of ISB 1342 (Part 1 and Part 2)
timeFrame: 28 days
measure: Immunogenicity of ISB 1342 by anti-drug antibody (ADA) formation (Part 1 and Part 2)
timeFrame: 28 days
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)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (duration of response [DOR]) (Part 1 and Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (disease control rate [DCR]) (Part 1 and Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (time to minimal residual disease [MRD] negative status) (Part 1 and Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (progression free survival [PFS]) (Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (time to treatment failure [TTF]) (Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (time to disease progression [TTP]) (Part 2)
timeFrame: 28 days
measure: Efficacy of ISB 1342 (overall survival [OS]) (Part 2)
timeFrame: Time from first dose until death from any cause or end of study collection, whichever is later, assessed up to 60 months.
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)
timeFrame: 28 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center (MCCC) - Rochester
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
state: Cedex
city: Pessac
country: France
facility: CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
state: Cedex
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon-Sud
state: Cedex
city: Poitiers
country: France
facility: CHU de Poitiers
state: Cedex
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
state: Cedex
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
state: Cedex
city: Tours
country: France
facility: CHRU de Tours - Hôpital Bretonneau
state: Cedex
city: Créteil
country: France
facility: CHU Hôpital Henri Mondor
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
city: Marseille
country: France
facility: L'Institut Paoli - Calmettes
city: Paris
country: France
facility: Hôpital Saint-Antoine
Study officials:
References: