Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma

Relapsed/Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03309111
• Other study ID #: ISB 1342-101
• Secondary ID: 2016-005253-20
• Status: Recruiting
• Phase: Phase 1
• Start date: October 25, 2017
• Est. completion date: May 2024

Study information

• Verified date: May 2022
• Source: Ichnos Sciences SA
• Contact: Ichnos Sciences Clinical Trials Administrator
• Phone: (315) 583-1249
• Email: clinicaltrials[@]ichnossciences.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 245
• Est. completion date: May 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Biological:
• ISB 1342
ISB-1342 is CD38 x CD3 BEAT® 1.0 bispecific antibody. ISB 1342 is administered by intravenous (IV) infusion or subcutaneous injection (SC)

Locations

Country	Name	City	State
France	CHU Hôpital Henri Mondor	Créteil
France	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille
France	L'Institut Paoli - Calmettes	Marseille
France	CHU de Nantes - Hôtel-Dieu	Nantes	Cedex
France	Hôpital Saint-Antoine	Paris
France	CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque	Pessac	Cedex
France	Centre Hospitalier Lyon-Sud	Pierre Benite	Cedex
France	CHU de Poitiers	Poitiers	Cedex
France	CHU de Rennes - Hôpital Pontchaillou	Rennes	Cedex
France	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse	Cedex
France	CHRU de Tours - Hôpital Bretonneau	Tours	Cedex
United States	Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Duke Clinical Research Institute	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Arkansas for Medical Sciences (UAMS)	Little Rock	Arkansas
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	Mayo Clinic Cancer Center (MCCC) - Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Ichnos Sciences SA	Glenmark Pharmaceuticals S.A.

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal tolerated dose (MTD) and/or recommended part 2 dose (RP2D) of ISB 1342 (Part 1)		28 days
Primary	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	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
Secondary	Maximum serum concentration (Cmax) of ISB 1342 (Part 1 and Part 2)		28 days
Secondary	Time to reach maximum observed plasma concentration (Tmax) of ISB 1342 (Part 1 and Part 2)		28 days
Secondary	Area under the serum concentration time curve from zero to time t (AUC0-t) of ISB 1342 (Part 1 and Part 2)		28 days
Secondary	Area under the curve from time zero to end of dosing interval (AUC0-tau) of ISB 1342 (Part 1 and Part 2)		28 days
Secondary	Immunogenicity of ISB 1342 by anti-drug antibody (ADA) formation (Part 1 and Part 2)		28 days
Secondary	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
Secondary	Efficacy of ISB 1342 (duration of response [DOR]) (Part 1 and Part 2)		28 days
Secondary	Efficacy of ISB 1342 (disease control rate [DCR]) (Part 1 and Part 2)		28 days
Secondary	Efficacy of ISB 1342 (duration of disease control) (Part 1 and Part 2)		28 days
Secondary	Efficacy of ISB 1342 (time to minimal residual disease [MRD] negative status) (Part 1 and Part 2)		28 days
Secondary	Efficacy of ISB 1342 (progression free survival [PFS]) (Part 2)		28 days
Secondary	Efficacy of ISB 1342 (time to treatment failure [TTF]) (Part 2)		28 days
Secondary	Efficacy of ISB 1342 (time to disease progression [TTP]) (Part 2)		28 days
Secondary	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.
Secondary	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