Advanced Biliary Cancer, Pancreatic Cancer
Conditions
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
Interventions
DRUGanti-EX02 CAR T cells
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
Sponsors
Zeno Therapeutics Pte. Ltd
Zhang Xiaofeng,MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1\) 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): 1. Neutrophil count ≥ 1.5×10\^9/L 2. Hemoglobin ≥ 90g/L 3. Platelet count ≥ 100×10\^9/L 4. Lymphocyte count ≥ 0.5×10\^9/L 10) Adequate liver, kidney, heart and lung functions at least indicated by: <!-- --> 1. Creatinine clearance ≥ 60ml/min 2. ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved) 3. LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam 4. 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
Exclusion criteria
* 28 participants fulfilling the following criteria will be enrolled. Inclusion criteria: 1. 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): 1. Neutrophil count ≥ 1.5×10\^9/L 2. Hemoglobin ≥ 90g/L 3. Platelet count ≥ 100×10\^9/L 4. Lymphocyte count ≥ 0.5×10\^9/L 10. Adequate liver, kidney, heart and lung functions at least indicated by: 1. Creatinine clearance ≥ 60ml/min 2. ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved) 3. LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of treatment-related adverse events (TEAEs) | 4 weeks after the first CAR-T cell infusion | 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). |
| Objective Response Rate | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 24 weeks | OS is the time between the date of first dose and the date of death due to any reason. |
| Progression Free Survival (PFS) | 24 weeks | PFS is the time between the date of first dose and the date of first documented disease progression as determined by the investigator using RECIST v1.1 or death due to any cause, whichever occurs first. |
| 5) Volume of ascites measured by ultrasonography and/or frequency and volume of ascites aspiration | 24 weeks | — |
| Disease control rate (DOC) | 24 weeks | DOC is the proportion of participants with a stable disease (SD) or an objective response (CR or 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. |
| Duration of Response (DOR) | 24 weeks | DOR is the time from onset of response to progression or death due to any reason, whichever occurs first. |
Contacts
Primary ContactXiaofeng Zhang
Backup ContactXiaofeng Zhang
Outcome results
None listed