GCC19CART for Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Study ICT-GCC19CART-US-001 (CARAPIA-1) is a Phase 1 study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of GCC19CART in subjects with relapsed or refractory metastatic colorectal cancer.

Official Title
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A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of GCC19CART for Subjects With Relapsed or Refractory Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: GCC19CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years old Clinical and histopathological diagnosis of metastatic colorectal cancer Guanylate Cyclase (GCC) positive disease as determined by immunohistochemistry (IHC). Positivity on staining of archival tumor tissue is adequate. Limited liver disease (less than 7 lesions with largest lesion less than 3 cm) No surgical options with curative intent. Received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in the advanced or metastatic setting, an anti-vascular endothelial growth factor (anti-VEGF) biological therapy if not contraindicated, and if RAS wild-type an anti-epidermal growth factor receptor (anti-EGFR) therapy in a manner consistent with National Comprehensive Cancer Network (NCCN) guidelines. Treatment must have been discontinued for disease progression or intolerance to therapy. Have at least one extracranial measurable target lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard. Exclusion Criteria: Subjects with tumor lesion(s) in a location that may cause perforation of an organ or structure (such as the digestive track, urinary bladder, or blood vessel) with GCC19CART therapy. No active infectious diseases or comorbid conditions that would interfere with safety or data quality. Subjects with active infection requiring systemic therapy or causing fever (temperature > 38.1˚C) or subjects with unexplained fever (temperature > 38.1˚C) within 7 days prior to enrollment (leukapheresis) and reconfirmed prior to the day of investigational product administration. Pregnant or breast-feeding women Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GCC19CART<br>Single infusion of GCC19CART at the dose assigned to an individual subject. All subjects will receive the same investigational therapy with the dose administered dependent upon the dose level they are assigned to in a sequential manner. Two dose level escalations are planned with one dose de-escalation listed if needed. | Drug: GCC19CART<br>* Single infusion of Chimeric Antigen Receptor (CAR) transduced autologous T cells administered intravenously (i.v.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study |  | Infusion (Day 0) up to Day 28 | 
| Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study |  | Infusion (Day 0) up to Day 28 | 
| Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study |  | Infusion (Day 0) up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response as measured by overall response rate based on the tumor size per Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 |  | Infusion (Day 0) up to approximately 12 months or until disease progression/recurrence | 
| Duration of Response (DOR) | The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). | Infusion (Day 0) up to approximately 12 months | 
| Progression Free Survival (PFS) | Progression free survival (PFS) time which is defined as time from date of leukapheresis until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first. | Day 30 (date of leukapheresis) up to approximately 13 months or until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first. | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from the date of leukapheresis until death from any cause. | Day 30 (date of leukapheresis) up to approximately 13 months or until death from any cause | 
| Copy number of Guanylate Cyclase C (GCC) by Quantitative Polymerase Chain Reaction (qPCR) |  | Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months) | 
| Copy number of each individual CD19 by Quantitative Polymerase Chain Reaction (qPCR) |  | Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months) | 
| Cytokine level in serum |  | Infusion (Day 0) up to 12 months post treatment | 
| AUC0 - Tmax: The area under curve (AUC) from time zero to Tmax in peripheral blood (days x copies/μg) |  | Infusion (Day 0) up to 12 months post treatment | 
| AUCTmax - 28d and/or AUCTmax - 84d: The area under curve (AUC) from time Tmax to day 28 and/or AUCTmax - 84d or other disease assessment days, in peripheral blood (days x copies/μg) |  | Infusion (Day 0) up to 12 months post treatment | 
| AUC0 - 28d and/or AUC0 - 84d: The area under curve (AUC) from time zero to day 28 and/or day 84 in peripheral blood (days x copies/μg) |  | Infusion (Day 0) up to 12 months post treatment | 
| Cmax: The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (copies/μg) |  | Infusion (Day 0) up to 12 months post treatment | 
| Tmax: The time to reach maximum(peak) in peripheral blood or other body fluid drug concentration after single dose administration (days) |  | Infusion (Day 0) up to 12 months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed metastatic colorectal cancer, refractory metastatic colorectal cancer, chimeric antigen receptors (CAR), colorectal cancer