Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (TRIgnite-1)

A Phase 1, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 2001 in Subjects With Relapsed/Refractory Multiple Myeloma

This study is a first-in-human, Phase 1, open-label study that will evaluate safety and anti-myeloma activity of ISB 2001 in participants with relapsed/refractory multiple myeloma (R/R MM).

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: ISB 2001; Drug: ISB 2001

Detailed Description

The study enrolls participants with R/R MM that have been treated with immunomodulatory drugs (IMiDs), proteasome inhibitors, and anti-CD38 therapies either in combination or as a single agent and are refractory to, or intolerant of, established therapies known to provide clinical benefit in MM.

The study is conducted in two parts: Part 1 dose escalation and Part 2 dose expansion.

Dose escalation continued until the maximum planned dose was reached. Dose expansion cohorts were initiated to further confirm safety and optimal biologically active dose. Participants receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment, or participant withdrawal from the study.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ichnos Sciences Clinical Trials Administrator; Phone Number: (315) 583-1249; Email: clinicaltrials@ichnossciences.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Hospital
      • Contact: Nicole Wong Doo; Phone Number: +61 2 9767 7243; Email: nicole.wongdoo@health.nsw.gov.au
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
      • Contact: Hanlon Sia, MBBS(Adelaide), FRACP, FRCPA; Email: drsia@fiho.com.au
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St. Vincent's Hospital Melbourne
      • Contact: Hang Quach; Phone Number: 03 9231 2003; Email: hang.quach@svha.org.au
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Center
      • Contact: Amit Khot; Phone Number: +6138559500; Email: Amit.Khot@petermac.org
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
      • Contact: Bradley Augustston; Phone Number: +61 (0) 8 6382 5100; Email: bradley.augustson@health.wa.gov.au
• France
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59800
      • Recruiting
      • CHRU Lille
      • Contact: Salomon Manier, MD; Phone Number: +33-320444292; Email: salomon.manier@chru-lille.fr
  • Nouvelle-Aquitaine
    • Poitiers, Nouvelle-Aquitaine, France, 86021
      • Recruiting
      • CHU Poiters - Hospital la Miletrie
      • Contact: Xavier Leleu, MD; Phone Number: +33-240083271; Email: xavier.leleu@chu-poitiers.fr
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44093
      • Recruiting
      • CHU de Nantes - Hotel Dieu
      • Contact: Cyrille Touzeau, MD; Phone Number: +33-240083271; Email: cyrille.touzeau@chu-nantes.fr
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75013
      • Recruiting
      • Groupe Hospitalier Pitie-Salpetriere
      • Contact: Laurent Garderet, MD; Phone Number: +33-611010920; Email: laurent.garderet@aphp.fr
• India
  • Bangalore, India
    • Active, not recruiting
    • HCG Hospital
  • Gujarat
    • Gandhinagar, Gujarat, India, 382428
      • Active, not recruiting
      • Apollo Hospital International Limited
  • Karnataka
    • Bangalore, Karnataka, India, 560027
      • Active, not recruiting
      • Health Care Global Enterprises Ltd.
  • Maharashta
    • Pune, Maharashta, India, 411004
      • Active, not recruiting
      • Deenanath Mangeshkar Hospital and Research Centre
  • Telangana
    • Hyderabad, Telangana, India, 500033
      • Active, not recruiting
      • Apollo Cancer Centers
• Italy
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • Active, not recruiting
      • ASST Spedali Civili Di Brescia
    • Milan, Lombardy, Italy, 20122
      • Recruiting
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
      • Contact: Matteo Da Via; Phone Number: +39-255033421; Email: matteo.davia@policlinico.mi.it
• Norway
  • Oslo County
    • Oslo, Oslo County, Norway, 0372
      • Recruiting
      • Oslo University Hospital
      • Contact: Fredrik Schjesvild, MD; Phone Number: +47-02770; Email: fredrikschjesvold@gmail.com
• Spain
  • Castile de Leon
    • Salamanca, Castile de Leon, Spain, 37007
      • Recruiting
      • Instituto de Investigacion Biomedica de Salamanca (IBSAL)
      • Contact: Maria-Victoria Mateos, MD; Phone Number: +34-923291100; Email: mvmateos@usal.es
  • Catalonia
    • Badalona, Catalonia, Spain, 08916
      • Recruiting
      • Institut Catala de Oncologia (ICO)
      • Contact: Laura Abril, MD; Phone Number: +34-934978706; Email: labril@iconcologia.net
    • Barcelona, Catalonia, Spain, 08036
      • Recruiting
      • Hospital Clinic De Barcelona
      • Contact: Laura Rosinol, MD; Phone Number: +34-932275428; Email: lrosinol@clinic.cat
  • Madrid
    • Madrid, Madrid, Spain, 28050
      • Active, not recruiting
      • Centro Integral Oncologici Clara Campal
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Nevarra
      • Contact: Paula Rodriguez Otero, MD; Phone Number: +34-948296397; Email: paurodriguez@unav.es
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Standford Cancer Institute
      • Contact: Michaela Liedtke; Phone Number: 650-723-0501; Email: mliedtke@stanford.edu
  • Florida
    • Miami, Florida, United States, 33136
      • Active, not recruiting
      • Sylvester Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute
      • Contact: Nishi Shah, MD; Phone Number: 404-778-0659; Email: nishi.nilesh@emory.edu
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Benjamin Derman, MD; Phone Number: 8472758131; Email: bendermanmd@gmail.com
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Shonali Midha, MD; Phone Number: 617-632-2104; Email: shonali_midha@dfci.harvard.edu
  • New York
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
      • Contact: David Levitz; Phone Number: 860-918-6192; Email: dlevitz@montefiore.org
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina
      • Contact: Eben Lichtman; Phone Number: 6178426051; Email: eben_lichtman@med.unc.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Tennessee Oncology
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Active, not recruiting
      • Virginia Commonwealth University (VCU)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin
      • Contact: Binod Dhakal, MD; Phone Number: 4148054600; Email: bdhakal@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants with pathologically confirmed MM with measurable M-protein: serum and/or 24 hour urine, serum-free light chains or measurable isolated plasmacytoma
2. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
3. Must have adequate hematologic, hepatic, renal, and cardiac functions

Exclusion Criteria:

1. Active malignant central nervous system involvement
2. Uncontrolled infection requiring systemic antibiotic therapy or other serious infection prior to C1D1
3. History of autoimmune disease requiring systemic immunosuppressive therapy
4. Any concurrent or uncontrolled medical, comorbid, psychiatric or social condition that would limit compliance with study procedures, interfere with the study results, substantially increase the risk of AEs, compromise ability to provide written informed consent or, in the opinion of the Investigator, constitute a hazard for participating in this study.
5. Female subjects who are lactating and breastfeeding or have a positive pregnancy test during the screening period or on Day 1 before first dose of ISB 2001.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants with R/R MM is administered ISB 2001 weekly on Days 1, 8, 15, and 22 of each 28-day cycle, with an additional step-up dose in Cycle 1 on Day 4. Treatment cycle duration is 28 days. Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment or participant withdrawal from the study	Drug: ISB 2001; Participants receive escalating doses of ISB 2001; Drug: ISB 2001; Participants receive injection of ISB 2001 as determined in Part 1.
Experimental: Part 2: Dose Expansion; Dose expansion cohorts are initiated to further confirm safety and optimal biologically active dose. Participants will receive ISB 2001 until disease progression, unacceptable toxicity occurs, any criterion for stopping the study treatment or participant withdrawal from the study.	Drug: ISB 2001; Participants receive escalating doses of ISB 2001; Drug: ISB 2001; Participants receive injection of ISB 2001 as determined in Part 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs)	Up to 18 months
Number of Dose-Limiting Toxicities (DLT) During the First 28 Days After the First Administration of ISB 2001 (Cycle 1) in Each Cohort (Part 1)	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	18 months
Progression Free Survival (PFS)	18 months
Maximum Concentration (Cmax) of ISB 2001 in Serum	Up to 28 days
Time to Reach Maximum Concentration (Tmax) of ISB 2001 in Serum	Up to 28 days
Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB 2001 in Serum	Up to 28 days
Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 2001 in Serum	Up to 28 days
Percent Incidence of Anti-Drug Antibody (ADA), Neutralizing Antibody (nAb) and Titer of ADA From Baseline Until End-of-Treatment (EOT)	Baseline to 18 months
Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG)	18 months
Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG)	18 months
Duration of Response (DOR) Based on International Myeloma Working Group (IMWG)	18 months
Time to Progression (TTP)	18 months
Time to Next Treatment (TTNT)	18 months
Time to Response (TTR)	18 months

Collaborators and Investigators

• Sponsor: Ichnos Sciences SA

Publications and helpful links

General Publications

• Carretero-Iglesia L, Hall OJ, Berret J, Pais D, Estoppey C, Chimen M, Monney T, Loyau J, Dreyfus C, Macoin J, Perez C, Menon V, Gruber I, Laurendon A, Caro LN, Gudi GS, Matsuura T, van der Graaf PH, Blein S, Mbow ML, Croasdale-Wood R, Srivastava A, Dyson MR, Matthes T, Kaya Z, Edwards CM, Edwards JR, Maiga S, Pellat-Deceunynck C, Touzeau C, Moreau P, Konto C, Drake A, Zhukovsky EA, Perro M, Pihlgren M. ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells. Nat Cancer. 2024 Oct;5(10):1494-1514. doi: 10.1038/s43018-024-00821-1. Epub 2024 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 7, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Open-label; Dose escalation; Dose expansion; Relapsed/refractory multiple myeloma; ISB 2001
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: ISB 2001-101

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