MOv19-BBz CAR T Cells in FRa+ Cancers

Официальное название

Phase I Clinical Trial of Autologous Folate Receptor-Alpha Redirected T Cells in Patients With FRa+ Cancers

Обзор

This is a Phase I open-label clinical trial to assess the safety, feasibility, and preliminary efficacy of intrapleural administration of MOv19-BBz CAR T cells in patients with FRa+ cancers. This study will be initiated in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) only. Subjects will receive a single dose of MOv19-BBz CAR T cells via intrapleural infusion following lymphodepleting chemotherapy. Subjects without an existing intra-pleural catheter will have a temporary pleural catheter placed for the study. Subjects may initiate treatment with commercial checkpoint inhibitors per routine care beginning at least 28 days after receiving MOv19-BBz CAR T cells.

Вмешательства

• Биопрепарат MOv19-BBz CAR T cells
  Autologous T cells engineered to express an extracellular single chain variable fragment (scFv) with FRa specificity.
• Препарат Cyclophosphamide/Fludarabine
  Cytotoxic chemotherapy agents used for lymphodepletion prior to MOv19-BBz CAR T cell administration.
• Устройство FRa Expression Testing
  Laboratory Developed Test used to determine subject eligibility

Первичные конечные точки

• Incidence of adverse events as assessed by CTCAE V5.0 [Срок оценки: Up to 15 years post-MOv19-BBz CAR T cell administration]
• Occurrence of treatment-limiting toxicities (TLTs) [Срок оценки: 28 days post-MOv19-BBz CAR T cell administration]

Вторичные конечные точки (5)

• Evaluate study feasibility [Срок оценки: 6 months]
• Objective Response Rate (ORR) [Срок оценки: Up to 12 months following treatment with MOv19-BBz CAR T cells]
• Duration of Response (DOR) [Срок оценки: Up to 15 years following treatment with MOv19-BBz CAR T cells]
• Progression Free Survival (PFS) [Срок оценки: Up to 15 years following treatment with MOv19-BBz CAR T cells]
• Overall Survival (OS) [Срок оценки: Up to 15 years following treatment with MOv19-BBz CAR T cell]

Критерии участия

Критерии включения

• Signed informed consent form
• Documentation of tumor FRa expression by IHC at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available.
• Disease-specific criteria:

a. NSCLC Patients: i. Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion.

ii. Failure of at least one prior line of standard of care therapy for advanced stage disease.

• Patients must have evidence of active disease as defined by RECIST 1.1 criteria
• Patients with asymptomatic CNS metastases that have been treated (and are off steroids for the treatment of CNS disease) are allowed. They must meet the following criteria

• No concurrent treatment for the CNS disease
• No progression of CNS metastasis on MRI at screening
• No evidence of leptomeningeal disease or cord compression
• Adequate organ function defined as:

• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; Patient must not be on dialysis
• ALT/AST ≤ 3x upper limit of normal range
• Serum total bilirubin ≤ 1.5 mg/dl, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤ 3.0 mg/dl)
• Must have a minimum level of pulmonary reserve defined as < Grade 1 dyspnea and pulse oxygen > 92% on room air
• Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO or MUGA
• Male or female age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
• Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.

Критерии исключения

• Any clinically significant pleural effusion that cannot be drained with standard approaches.
• Patients with significant lung disease as follows:

• Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.Note: "Greater than lobar" = "in more than 1 lobe".
• Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
• Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.).
• Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
• Dependence on systemic steroids or immunosuppressant medications.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pennsylvania — Philadelphia

Идентификаторы

NCT: NCT07116057 · 858800 (UPCC #06525) · R01CA260902

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗