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

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

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.

Study Overview

• Status: Completed
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Biological: ISB 1342

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 Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • CHU Hôpital Henri Mondor
  • Lille, France, 59000
    • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez
  • Marseille, France, 13009
    • L'Institut Paoli - Calmettes
  • Paris, France, 75012
    • Hôpital Saint-Antoine
  • Cedex
    • Nantes, Cedex, France, 44093
      • CHU de Nantes - Hotel-Dieu
    • Pessac, Cedex, France, 33604
      • CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque
    • Pierre Benite, Cedex, France, 69495
      • Centre Hospitalier Lyon-Sud
    • Poitiers, Cedex, France, 86021
      • CHU de Poitiers
    • Rennes, Cedex, France, 35033
      • CHU de Rennes - Hôpital Pontchaillou
    • Toulouse, Cedex, France
      • Institut Universitaire du Cancer de Toulouse - Oncopole
    • Tours, Cedex, France, 37044
      • CHRU de Tours - Hôpital Bretonneau
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medicine - The Sidney Kimmel Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center (MCCC) - Rochester
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Beth Israel
  • North Carolina
    • Durham, North Carolina, United States, 72205
      • Duke Clinical Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Ichnos Sciences SA
• Collaborators: Glenmark Pharmaceuticals S.A.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2017
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: October 4, 2017
• First Submitted That Met QC Criteria: October 12, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 12, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ISB 1342-101; 2016-005253-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No