Squamous Cell Lung Cancer
Conditions
Keywords
squamous cell lung cancer, advanced squamous cell lung cancer, metastatic squamous cell lung cancer
Brief summary
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.
Interventions
DRUGC-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).
Sponsors
Shanghai AbelZeta Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE/SAE/AESI, DLT | From baseline to 28 days after treatment | * To assess the safety and tolerability of C-CAR031 in participants * To determine the RDE (Phase Ia) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR (Objective Response Rate) | From baseline until disease progression likely at 12 months | To estimate the anti-tumor activity of C-CAR031 in participants with GPC3+ advanced/metastatic squamous cell lung cancer |
| CK Parameter and Quantification of CAR copies/μg DNA of C-CAR031 | From baseline until 15 years of infusion as longest | To investigate the CK of C-CAR031 |
| Presence of RCL | From baseline until 15 years of infusion as longest | To assess the safety of C-CAR031 |
| DCR (Disease Control Rate) | From baseline until disease progression likely at 12 months after treatment | To estimate the anti-tumor activity of C-CAR031 in participants with GPC3+ advanced/metastatic squamous cell lung cancer |
| DoR (Duration of Response) | From baseline until disease progression likely at 12 months after treatment | — |
| DRR (Durable Response Rate) | From baseline until disease progression likely at 12 months after treatment | — |
| TTR (Time to Response) | From baseline until disease progression likely at 12 months after treatment | — |
| PFS (Progression-free Survival) | From baseline until disease progression likely at 12 months after treatment | — |
| Change in tumor size | From baseline until disease progression likely at 12 months after treatment | — |
Countries
China
Contacts
CONTACTYinghua Shen
PRINCIPAL_INVESTIGATORShun Lu, MD
Shanghai Chest Hospital, China
Outcome results
None listed