An Phase I Trial of a CAR T-cell Infusion C-CAR031 in Participants With GPC3+ Advanced/Metastatic Squamous Cell Lung Cancer

Официальное название

An Investigator-initiated Phase I Trial of an Armored and GPC3-targeted Autologous CAR T-cell Infusion C-CAR031 in Participants With GPC3+ Advanced/Metastatic Squamous Cell Lung Cancer

Обзор

This single-arm, open-label, multicenter, Phase I study will evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics (PK)/pharmacodynamics (PD), biomarker, and immunogenicity of C-CAR031 in adult participants with GPC3+ advanced/metastatic squamous cell lung cancer, who are not amenable to curative therapy and have progressed or are intolerant to no more than 3 lines of prior systemic treatment including immune checkpoint inhibitors (CPIs) and platinum-based doublet chemotherapy, concurrently or sequentially.

Вмешательства

• Препарат C-CAR031
  C-CAR031 is an autologous CAR T-cell product that expresses a CAR specific for GPC3 and a dominant-negative transforming growth factor-beta receptor II (dnTGFβRII).

Первичные конечные точки

• AE/SAE/AESI, DLT [Срок оценки: From baseline to 28 days after treatment]

Вторичные конечные точки (9)

• ORR (Objective Response Rate) [Срок оценки: From baseline until disease progression likely at 12 months]
• CK Parameter and Quantification of CAR copies/μg DNA of C-CAR031 [Срок оценки: From baseline until 15 years of infusion as longest]
• Presence of RCL [Срок оценки: From baseline until 15 years of infusion as longest]
• DCR (Disease Control Rate) [Срок оценки: From baseline until disease progression likely at 12 months after treatment]
• DoR (Duration of Response) [Срок оценки: From baseline until disease progression likely at 12 months after treatment]
• DRR (Durable Response Rate) [Срок оценки: From baseline until disease progression likely at 12 months after treatment]
• TTR (Time to Response) [Срок оценки: From baseline until disease progression likely at 12 months after treatment]
• PFS (Progression-free Survival) [Срок оценки: From baseline until disease progression likely at 12 months after treatment]
• Change in tumor size [Срок оценки: From baseline until disease progression likely at 12 months after treatment]

Критерии участия

Критерии включения

• Histologically or cytologically confirmed unresectable Stage IIIB ,IIIC or IV squamous cell lung cancer
• Confirmed to express GPC3, as assessed by immunohistochemistry at a central lab
• Participants who have progressed or intolerant to no more than three lines of prior systemic therapies for advanced/metastatic squamous cell lung cancer
• At least one measurable target lesion
• The left ventricular ejection fraction (LVEF) measured by echocardiography ≥50% and reported as non-impaired.
• Sufficient pulmonary function
• The laboratory testing results meet the study requirements
• Female participants of childbearing potential must test negative for pregnancy in serum or urine. Non-sterilized participants (males and females) agree to take effective contraceptive measures for at least 12 months and until CAR-T below lower limit of detection (LLOD) by PCR which occurs last after C-CAR031 infusion.

Критерии исключения

• known to harbor a driver mutation for which targeted standard therapy is recommended in accordance with local treatment guidelines.
• Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO)
• Contraindication to lymphodepleting agents, including fludarabine and/or cyclophosphamide.
• History of splenectomy or organ transplantation
• Prior treatment with Any CAR-T therapy OR any therapy that is targeting GPC3
• Uncontrolled or intercurrent pulmonary disease
• Clinically meaningful ascites
• Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures
• Cancer-related spinal cord compression, leptomeningeal disease, or brain metastases
• Received radiation therapy, local treatment, vaccine, blood transfusion, systemic treatment within certain period of apheresis required by study protocol
• History of or with active diseases or conditions of that's defined in study protocol

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

Китай · 1 центр

• Shanghai Chest Hospital — Шанхай

Идентификаторы

NCT: NCT07444281 · 0926-045

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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