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

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

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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