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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат ISB 2001
  Participants receive escalating doses of ISB 2001
• Препарат ISB 2001
  Participants receive injection of ISB 2001 as determined in Part 1.

Первичные конечные точки

• Frequency and Severity Of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: 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) [Срок оценки: Up to 28 days]

Вторичные конечные точки (12)

• Maximum Concentration (Cmax) of ISB 2001 in Serum [Срок оценки: Up to 28 days]
• Time to Reach Maximum Concentration (Tmax) of ISB 2001 in Serum [Срок оценки: Up to 28 days]
• Area Under the Concentration Time Curve in Dosing Intervals (AUC0-tau) of ISB 2001 in Serum [Срок оценки: Up to 28 days]
• Area Under the Concentration Time Curve From Zero to Time t (AUC0-t) of ISB 2001 in Serum [Срок оценки: 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) [Срок оценки: Baseline to 18 months]
• Overall Response Rate (ORR) Based on International Myeloma Working Group (IMWG) [Срок оценки: 18 months]
• Complete Response Rate (CRR) Based on International Myeloma Working Group (IMWG) [Срок оценки: 18 months]
• Duration of Response (DOR) Based on International Myeloma Working Group (IMWG) [Срок оценки: 18 months]
• Time to Progression (TTP) [Срок оценки: 18 months]
• Time to Next Treatment (TTNT) [Срок оценки: 18 months]
• Time to Response (TTR) [Срок оценки: 18 months]
• Progression Free Survival (PFS) [Срок оценки: 18 months]

Критерии участия

Критерии включения

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

Критерии исключения

• Active malignant central nervous system involvement
• Uncontrolled infection requiring systemic antibiotic therapy or other serious infection prior to C1D1
• History of autoimmune disease requiring systemic immunosuppressive therapy
• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Standford Cancer Institute — Palo Alto
• Sylvester Cancer Center — Miami
• Winship Cancer Institute — Atlanta
• University of Chicago Medical Center — Chicago
• Beth Israel Deaconess Medical Center — Boston
• Montefiore Medical Center — The Bronx
• University of North Carolina — Chapel Hill
• Tennessee Oncology — Nashville
• … и ещё 2 центра

Австралия · 5 центров

• Concord Hospital — Concord
• Pindara Private Hospital — Benowa
• St. Vincent's Hospital Melbourne — Fitzroy
• Peter MacCallum Cancer Center — Melbourne
• Linear Clinical Research — Nedlands

Индия · 5 центров

• Apollo Hospital International Limited — Gandhinagar
• Health Care Global Enterprises Ltd. — Bangalore
• Deenanath Mangeshkar Hospital and Research Centre — Pune
• Apollo Cancer Centers — Hyderabad
• HCG Hospital — Bangalore

Испания · 5 центров

• Instituto de Investigacion Biomedica de Salamanca (IBSAL) — Salamanca
• Institut Catala de Oncologia (ICO) — Badalona
• Hospital Clinic de Barcelona — Barcelona
• Centro Integral Oncologici Clara Campal — Madrid
• Clinica Universidad de Nevarra — Pamplona

Франция · 4 центра

• CHRU Lille — Lille
• CHU Poiters - Hospital la Miletrie — Poitiers
• CHU de Nantes - Hotel Dieu — Nantes
• Groupe Hospitalier Pitie-Salpetriere — Paris

Италия · 2 центра

• ASST Spedali Civili di Brescia — Brescia
• Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico — Milan

Норвегия · 1 центр

• Oslo University Hospital — Oslo

Публикации

• 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, Pihlgr PMID 39261676

Идентификаторы

NCT: NCT05862012 · ISB 2001-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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