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

Sponsor

Ichnos Sciences SA (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03309111

Collaborator

Glenmark Pharmaceuticals S.A. (Industry)

245

Enrollment

Locations

Arm

78.2

Anticipated Duration (Months)

11.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Biological: ISB 1342	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

245 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 25, 2017

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ISB 1342 Part 1: Cohorts of multiple ISB 1342 dose levels; Part 2: One dose regimen until disease progression or other discontinuation criterion is met	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)

Arm

Intervention/Treatment

Experimental: ISB 1342

Part 1: Cohorts of multiple ISB 1342 dose levels; Part 2: One dose regimen until disease progression or other discontinuation criterion is met

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)

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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]
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]
Efficacy of ISB 1342 (duration of disease control) (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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences (UAMS)	Little Rock	Arkansas	United States	72205
2	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
3	Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
4	Mayo Clinic Cancer Center (MCCC) - Rochester	Rochester	Minnesota	United States	55905
5	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	Mount Sinai Beth Israel	New York	New York	United States	10029
7	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
8	Duke Clinical Research Institute	Durham	North Carolina	United States	72205
9	Tennessee Oncology	Nashville	Tennessee	United States	37203
10	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
11	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
12	CHU de Nantes - Hôtel-Dieu	Nantes	Cedex	France	44093
13	CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque	Pessac	Cedex	France	33604
14	Centre Hospitalier Lyon-Sud	Pierre Benite	Cedex	France	69495
15	CHU de Poitiers	Poitiers	Cedex	France	86021
16	CHU de Rennes - Hôpital Pontchaillou	Rennes	Cedex	France	35033
17	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse	Cedex	France
18	CHRU de Tours - Hôpital Bretonneau	Tours	Cedex	France	37044
19	CHU Hôpital Henri Mondor	Créteil		France	94010
20	Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez	Lille		France	59000
21	L'Institut Paoli - Calmettes	Marseille		France	13009
22	Hôpital Saint-Antoine	Paris		France	75012

Sponsors and Collaborators

Ichnos Sciences SA
Glenmark Pharmaceuticals S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ichnos Sciences SA

ClinicalTrials.gov Identifier:

NCT03309111

Other Study ID Numbers:

ISB 1342-101
2016-005253-20

First Posted:

Oct 13, 2017

Last Update Posted:

May 16, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Study Results

No Results Posted as of May 16, 2022