Limited-duration Teclistamab

Официальное название

Phase 2, Single-Arm, Non-Inferiority Study Of Limited-Duration Teclistamab For Relapsed Refractory Multiple Myeloma

Обзор

This is a single-arm, non-inferiority study in which patients who have achieved a very good partial response (VGPR) or better, according to International Myeloma Working Group (IMWG) response criteria, following 6 to 9 months of treatment with teclistamab, a B-cell maturation antigen (BCMA)-directed T-cell engager (anti-BCMAxCD3 bispecific antibody), will be offered monitored drug discontinuation. Teclistamab is typically dosed on a regular schedule (every 1-4 weeks) indefinitely until disease progression ("continuous therapy"). Here, a limited-duration regimen will be studied in which patients achieving ≥VGPR after 6-9 months of standard teclistamab dosing will discontinue therapy and resume if laboratory or clinical parameters suggest early disease progression ("limited-duration therapy"). Patients will enter the clinical trial protocol after completing 6-9 months of standard teclistamab monotherapy and achieving ≥VGPR. The study's hypothesis is that the failure probability six months after stopping teclistamab in this patient population will be non-inferior compared to that of historical controls treated with continuous therapy. Reducing drug exposure may be beneficial by reducing risk of infection and reducing anti-BCMA selective pressure toward generation of BCMA-negative relapses. Analysis of minimal residual disease (MRD), tumor features, and bone marrow microenvironment parameters, which will be pursued as exploratory correlative analyses in this study, may identify factors that predict durable response to limited-duration therapy and thereby enable more precise selection of patients likely to benefit from this approach. A subset of patients will be enrolled on a biomarker study for analysis of these exploratory endpoints.

Вмешательства

• Другое Off Drug Surveillance
  After stopping teclistamab, participants will be monitored monthly by standard serum paraprotein studies for disease progression. Participants will resume teclistamab at time of disease progression. After Teclistamab therapy re-initiation on-study, monthly response assessments and data for other study endpoints will be obtained. All participants will undergo peripheral blood collection for correlative research studies at baseline and every two months on-study. Participants who enroll on the biom

Первичные конечные точки

• Failure free at six months following teclistamab discontinuation [Срок оценки: Six months after teclistamab discontinuation]

Вторичные конечные точки (8)

• Time to progression and progression-free survival [Срок оценки: Two years after teclistamab discontinuation.]
• Time-to-treatment failure [Срок оценки: Two years after teclistamab discontinuation]
• Re-initiation rate [Срок оценки: Six months after teclistamab discontinuation]
• Rate of response to teclistamab re-initiation [Срок оценки: Two years after teclistamab discontinuation]
• Rate of infectious complications [Срок оценки: 12 months after teclistamab discontinuation]
• Rate and type of clinical complications of progressive disease [Срок оценки: Six months after teclistamab discontinuation]
• Quality of life [Срок оценки: Two years after teclistamab discontinuation]
• Mean percent change in peripheral blood studies [Срок оценки: Two years after teclistamab discontinuation]

Критерии участия

Критерии включения

• Participants must be age ≥18 and able to give written, informed consent.
• Participants must have initiated teclistamab (first full dose) 6-9 months prior to enrollment and received an average teclistamab dose of at least 1.5 mg/kg/month since the date of the first 1.5 mg/kg dose.
• Participants must have received a teclistamab dose within 4 weeks prior to enrollment.
• Participants must have had measurable disease according to IMWG criteria within 1 month prior to teclistamab initiation or first full teclistamab dose
• Participants must have achieved a confirmed VGPR or better to teclistamab therapy at any assessment prior to enrollment and have ongoing response (i.e., no disease progression) at time of enrollment per IMWG consensus criteria (Appendix 14.3).
• Prior to initiating teclistamab, participants must have received therapy with a proteasome inhibitor, thalidomide analog (lenalidomide or pomalidomide), and an anti-CD38 antibody and meet one of the following criteria:

• ≥3 prior lines of therapy (with lines-of-therapy delineated according to IWMG guidelines)
• Refractory to both a proteasome inhibitor and a thalidomide analog.
• Participants must have had an ECOG performance status of 0-2 at time of teclistamab initiation; in addition, ECOG performance status must be 0-1 at time of enrollment.
• Participants must not have known diagnoses of systemic amyloidosis or POEMS syndrome.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 5 центров

• University of Arkansas for Medical Sciences — Little Rock
• University of Iowa Hospitals and Clinics — Iowa City
• Columbia University — New York
• Abramson Cancer Center at University of Pennsylvania — Philadelphia
• Thomas Jefferson University, Honickman Center — Philadelphia

Публикации

• Razzo BM, Midha S, Portuguese AJ, Grajales-Cruz AF, De Menezes Silva Corraes A, Costello P, Liu Y, Sperling AS, Nadeem O, Dima D, Banerjee R, Cowan AJ, Afrough A, Anderson LD Jr, Lieberman-Cribbin A, Kaur G, Goyal A, Atrash S, Ferreri CJ, Voorhees PM, Pasvolsky O, Lee HC, Patel KK, Julian KL, Forsberg PA, Herr MM, Chhabra S, Parrondo RD, Lin Y, Chen A, Susanibar-Adaniya SP, Khouri J, Raza S, Anwer PMID 40629516

Идентификаторы

NCT: NCT05932680 · UPCC 08423 · IRB 853459

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗