SynKIR-310 for Relapsed/Refractory B-NHL

Официальное название

A Phase 1 Study of SynKIR-310, Autologous T Cells Transduced With CD19 KIR-CAR, in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Обзор

This first-in-human (FIH) trial is designed to assess the safety, feasibility and preliminary efficacy of a single intravenous (IV) dose of SynKIR-310 administered to participants with relapsed/refractory B-NHL.

Подробное описание

This is a Phase 1, FIH, multicenter, open-label study of a single infusion of SynKIR-310 in participants with relapsed/refractory B-NHL.

Up to 36 participants, regardless of subtypes of B-NHL, who meet the eligibility criteria, will be treated in the study.

Up to 4 cohorts of 3 to 6 participants per cohort will be assessed to determine the safety and feasibility of treatment with SynKIR-310. Doses will be escalated across up to 4 cohorts to determine a Recommended Phase 2 Dose (RP2D).

Once the RP2D has been determined, a dose expansion group will enroll additional participants regardless of subtypes of B-NHL at the RP2D to further characterize the safety, feasibility and preliminary efficacy of SynKIR-310 in treating B-NHL.

Вмешательства

• Биопрепарат SynKIR-310
  Autologous T Cells transduced with CD19 KIR-CAR

Первичные конечные точки

• Evaluate the safety of SynKIR310 [Срок оценки: Up to 24 months]
• Recommended Phase 2 Dose (RP2D) [Срок оценки: Up to 24 months]

Вторичные конечные точки (5)

• Feasibility of SynKIR-310 [Срок оценки: Up to 24 months]
• Preliminary efficacy : Objective response rate (ORR) [Срок оценки: Up to 24 months]
• Preliminary efficacy: Complete response rate (CR) [Срок оценки: Up to 24 months]
• Preliminary efficacy: Duration of response (DOR) [Срок оценки: Up to 24 months]
• PK profile of SynKIR-310 [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• Adult 18 years of age and older.
• Histologically confirmed diagnosis of B-NHL before enrollment.
• Must have received prior CAR T or were unwilling/unable to receive prior CAR T.
• Must have refractory or relapsed disease after receiving 2 prior lines of therapies.
• If relapsed/refractory post-auto-SCT, then must have undergone auto-SCT at least 6 months prior to enrollment.
• If relapsed/refractory disease after allogeneic stem cell transplant (allo SCT) then must have undergone allo-SCT at least 6 months prior to enrollment and without evidence of graft versus host disease, and expectation to remain off immunosuppressive therapy through duration of trial
• Measurable disease at time of enrollment: At least one measurable lesion per Lugano Response Criteria (Cheson et al., 2014) or measurable disease per IWWM-11 response criteria (Treon 2023) for Waldenström macroglobulinemia patients.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Критерии исключения

• Previously treated with any investigational agent within 30 days prior to screening.
• Any previous or concurrent malignancy, with the following exceptions:

Adequately treated non-melanoma skin cancer such as basal cell or squamous cell carcinoma; carcinoma-in-situ (e.g., cervix, bladder, breast) treated curatively and without evidence of recurrence for at least 3 years prior to enrollment or adequately treated melanoma skin cancer in-situ; any other malignancy which has been completely treated and remains in complete remission for ≥ 5 years prior to enrollment. Completely treated prostate cancer with prostate-specific antigen (PSA) level < 1.0 may also be permitted.

• Use of systemic immunosuppressive drugs within 4 weeks prior to study entry, or anticipated use of systemic immunosuppressive agents through end of study, with the exception of non-T cell targeting agents prior to leukapheresis
• Known immunodeficiency disease , with the exception of hypoglobulinemia
• History or presence of active or clinically relevant primary central nervous system (CNS) disorder, such as seizure, encephalopathy, cerebrovascular ischemia/hemorrhage, cerebellar disease, or any autoimmune disease with CNS involvement. For primary CNS disorders that have recovered or are in remission, participants without recurrence within 2 years of planned study enrollment may be included.
• Uncontrolled hypertension, history of myocarditis or congestive heart failure, unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction within 6 months prior to study entry.
• Any active uncontrolled systemic fungal, bacterial or viral infection.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

Лечение

Центры проведения

США · 5 центров

• Colorado Blood Cancer Institute, part of Sarah Cannon Cancer Institute — Denver
• Winship Cancer Institute of Emory University — Atlanta
• The University of Kansas Cancer Center — Fairway
• Rutgers Cancer Institute — New Brunswick
• Abramson Cancer Center of the University of Pennsylvania — Philadelphia

Идентификаторы

NCT: NCT06544265 · CELESTIAL-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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