A Study to Investigate the Safety and Efficacy of SAR446523 Injected Subcutaneously in Adult Participants With Relapsed/Refractory Myeloma

Официальное название

A First-in-human, Open-label, Phase 1 Study to Evaluate the Safety, Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of Subcutaneous SAR446523, an Anti-GPRC5D ADCC-enhanced Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma

Обзор

This is a first-in-human study of SAR446523 conducted in patients with RRMM. The study consists of two parts: Dose escalation (Part A): In this part, up to several dose levels (DLs) of SAR446523 will be explored to determine the maximum administered dose (MAD), maximum tolerated dose (MTD), and recommended dose range (RDR) of 2 dose regimens which will be tested in the dose optimization part. Dose optimization (Part B): In this part, participants will be randomly assigned in a 1:1 ratio using interactive response technology (IRT) to either one of the chosen dose regimens of SAR446523 (determined from data coming from Part A), to determine the optimal dose as the recommended phase 2 dose (RP2D) of SAR446523.

Подробное описание

The study will be considered ongoing until the last participant last visit has occurred. Participants will be allowed to continue therapy until disease progression, unacceptable AEs, participant or Investigator's request to discontinue treatment.

Вмешательства

• Препарат SAR446523
  Pharmaceutical form: Powder for solution for injection; Route of administration: Subcutaneous (SC)

Первичные конечные точки

• Incidence of Dose Limiting Toxicities (DLTs)- Dose escalation (Part A) [Срок оценки: Cycle 1 (28 days)]
• Overall response rate (ORR) - Dose optimization (Part B) [Срок оценки: 24 months after the Last Participant In (LPI)]

Вторичные конечные точки (12)

• Number of participants with treatment emergent adverse events (TEAEs), injection related reactions (IRRs), injection site reactions (ISRs), serious adverse events (SAEs), adverse event of special interests (AESIs) [Срок оценки: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years]
• Change from baseline in laboratory abnormalities [Срок оценки: From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 5 years]
• ORR- Dose escalation (Part A) [Срок оценки: 24 months after the Last Participant In (LPI)]
• VGPR or better rate [Срок оценки: 24 months after the Last Participant In (LPI)]
• Clinical benefit rate (CBR) [Срок оценки: 24 months after the Last Participant In (LPI)]
• Duration of response (DoR) [Срок оценки: 24 months after the Last Participant In (LPI)]
• Time to response (TTR) [Срок оценки: 24 months after the Last Participant In (LPI)]
• Progression free survival (PFS) [Срок оценки: 24 months after the Last Participant In (LPI)]
• Minimal residual disease (MRD) status negativity [Срок оценки: 24 months after the Last Participant In (LPI)]
• Number of participants with symptomatic AEs -Part B [Срок оценки: From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years]
• Change from baseline in overall side effect bother as measured by the Functional Assessment of Cancer Therapy item 5 (FACT-GP5)- Part B [Срок оценки: From Cycle 1 Day 1 to 30 days after the date of the last study treatment administration i.e., approximately 5 years]
• Maximum observed concentration (Cmax) [Срок оценки: Multiple timepoints from Cycle 1 Day 1 to Cycle 1 Day 8 (cycle 1=28 days)]

Критерии участия

Критерии включения

• Participants with a documented diagnosis of multiple myeloma (MM) with measurable disease.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Dose escalation (Part A)

• Participants must have received at least 3 prior lines of antimyeloma therapy, and must be either relapsed or refractory to the above therapies, or are intolerant to them.
• Note: In Part A, prior exposure to anti g-protein-coupled receptor, class c, group 5, member d (GPRC5D) therapy and anti B-cell maturation antigen (BCMA) therapy is allowed.

Dose optimization (Part B)

• Participants must have received at least 3 prior lines of antimyeloma therapy and be either relapsed or refractory to immunomodulator (IMiD), proteasome inhibitor (PI), anti CD38 monoclonal antibody (mAb), and anti BCMA targeting agent or are intolerant to them.
• Note: In Part B, prior exposure to antiGPRC5D therapy is not allowed.

Критерии исключения

-Participants are excluded from the study if any of the following criteria apply: Eastern cooperative oncology group performance status (ECOG PS) of 2 or greater.

• Primary systemic and localized amyloid light chain (AL) amyloidosis, active polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, active plasma cell leukemia. Participants with central nervous system involvement or with clinical signs of meningeal involvement of multiple myeloma.
• Systemic antimyeloma treatment within 14 days before the first study treatment administration.
• Prior treatment with natural killer (NK)-cell engaging therapy (such as monoclonal antibody with antibody-dependent cellular cytotoxicity as primary mechanism of action) within 90 days of the first study treatment administration.
• Inadequate organ and marrow function.
• Participants with significant concomitant illness.

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Mayo Clinic in Arizona - Phoenix- Site Number : 8400005 — Phoenix
• Mayo Clinic in Florida- Site Number : 8400003 — Jacksonville
• Mayo Clinic in Rochester - Minnesota- Site Number : 8400004 — Rochester
• Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400001 — Hackensack
• Thomas Jefferson University Hospital- Site Number : 8400002 — Philadelphia

Канада · 3 центра

• Investigational Site Number : 1240005 — Vancouver
• Investigational Site Number : 1240001 — Montreal
• Investigational Site Number : 1240002 — Sherbrooke

Израиль · 3 центра

• Investigational Site Number : 3760001 — Tel Aviv
• Investigational Site Number : 3760004 — Haifa
• Investigational Site Number : 3760002 — Jerusalem

Австралия · 2 центра

• Investigational Site Number : 0360001 — Wollongong
• Investigational Site Number : 0360002 — Melbourne

Франция · 2 центра

• Investigational Site Number : 2500002 — Lille
• Investigational Site Number : 2500001 — Nantes

Италия · 2 центра

• Investigational Site Number : 3800002 — Torette
• Investigational Site Number : 3800001 — Rozzano

Испания · 2 центра

• Investigational Site Number : 7240002 — Barcelona
• Investigational Site Number : 7240001 — Madrid

Идентификаторы

NCT: NCT06630806 · TED18162 · U1111-1301-4016 · 2024-511667-28

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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