Early Phase I Study of Autologous T Cells (EX02 CAR-T) for Unresectable Pancreatic/Bile Duct Cancer

NCT06196658 | Not Yet Recruiting Early Phase 1

• 1 other identifier: 20231226
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a early Phase 1 open-label study to explore the safety and possible efficacy of EX02 CAR T cell therapy in the treatment of patients with unresectable and/or metastatic pancreatic/bile duct cancer. Each participant will undergo leukapheresis after enrolment, receive treatment of the conditioning chemotherapy of cyclophosphamide and fludarabine, and an intra-tumoral injection or intraperitoneal infusion of Ex02 CAR T cells, probably followed by an intravenous infusion of EX02 CAR T cells. Each participant will proceed through the following study procedures:

• Screening
• Enrollment/Leukapheresis
• Conditioning chemotherapy
• CAR T treatment
• Post-treatment assessment
• Long-term follow-up

Conditions

Pancreatic Cancer; Advanced Biliary Cancer

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of treatment-related adverse events (TEAEs)

  Grade and type of toxicity per dose level; fraction of patients who experience toxicity (including allergic reactions to T cell infusions) of ≥ Grade 3 according to CTCAEv5.0, cytokine release syndrome (CRS) of ≥ Grade 3 according to ASTCT consensus and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

  4 weeks after the first CAR-T cell infusion

• Objective Response Rate

  Objective Response Rate (ORR) is the proportion of participants with an objective response (either a complete response \[CR\] or partial response \[PR\]) in participants who received at least 1 dose of EX02CART and at least the 6-week tumor evaluation as determined by the investigator according to RECIST v1.1.

  24 weeks

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  24 weeks

• Duration of Response (DOR)

  24 weeks

• Overall survival (OS)

  24 weeks

• Disease control rate (DOC)

  24 weeks

• 5) Volume of ascites measured by ultrasonography and/or frequency and volume of ascites aspiration

  24 weeks

Study Arms (1)

anti-EX02 CAR T cells

EXPERIMENTAL

Drug: anti-EX02 CAR T cells

Interventions

anti-EX02 CAR T cells DRUG

Conditioning chemotherapy: • Lymphodepletion regimen consisting of fludarabine 25 mg/m2/day and cyclophosphamide 250 mg/m2/day for 3 consecutive days, administered 48 hours before first administration of first time of intravenous or intraperitoneal infusion Investigational Product: • Regional administration: Acetaminophen 500mg orally and diphenhydramine 20mg intramuscularly (or other non-steroidal anti-inflammatory drugs and antihistamines) were given in advance on the day of administration (day 0). Intraperitoneal infusion or intra-tumoral injection of anti-EX02 CAR T cells, with dosage and method determined by the investigator • Intravenous administration: Single infusion of CAR-transduced autologous T cells administered intravenously at a target dose of 2 x 106 anti-EX02 CAR T cells/kg, 30 minutes after premedication with oral acetaminophen 500mg and intramuscular diphenhydramine 20mg

anti-EX02 CAR T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer 2) Ineligible for, refractory to or relapsed after first or second line of chemotherapy 3) Presence of at least one measurable target lesion according to RECIST v1.1 4) EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells) 5) Male or female, ≥18 years 6) ECOG performance status 0 to 1 7) Expected life expectancy \>3 months 8) Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential 9) Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
• Neutrophil count ≥ 1.5×10\^9/L
• Hemoglobin ≥ 90g/L
• Platelet count ≥ 100×10\^9/L
• Lymphocyte count ≥ 0.5×10\^9/L 10) Adequate liver, kidney, heart and lung functions at least indicated by:
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• Creatinine clearance ≥ 60ml/min
• ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved)
• LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam
• No or only small amount of pleural fluid or ascites; blood oxygen saturation ≥ 95% 11) Voluntary participation in the trial and signing informed consent form

You may not qualify if:

• participants fulfilling the following criteria will be enrolled.
• Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer
• Ineligible for, refractory to or relapsed after first or second line of chemotherapy
• Presence of at least one measurable target lesion according to RECIST v1.1
• EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells)
• Male or female, ≥18 years
• ECOG performance status 0 to 1
• Expected life expectancy \>3 months
• Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential
• Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
• Neutrophil count ≥ 1.5×10\^9/L
• Hemoglobin ≥ 90g/L
• Platelet count ≥ 100×10\^9/L
• Lymphocyte count ≥ 0.5×10\^9/L
• Adequate liver, kidney, heart and lung functions at least indicated by:

Sponsors & Collaborators

• Zhang Xiaofeng,MD: lead
• Zeno Therapeutics Pte. Ltd: collaborator

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

Xiaofeng Zhang

CONTACT

057156005600; zxf837@tom.com

Xiaofeng Zhang

CONTACT

057156005600

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: December 26, 2023
• First Posted: January 9, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 9, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share