GC203 tumor-infiltrating lymphocyte therapy for pancreatic ductal adenocarcinoma

A Phase I Study of Engineered Tumor Infiltrating Lymphocytes Injection (GC203 TIL) in Patients With Pancreatic Ductal Adenocarcinoma

This trial will test whether gene-edited tumor-infiltrating lymphocytes (GC203 TIL), given after mild lymphodepletion, are safe and can help people with pancreatic ductal adenocarcinoma who have not responded to standard treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai Juncell Therapeutics (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Prednisone, cyclophosphamide
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06828328 on ClinicalTrials.gov

What this trial studies

This early-phase 1 interventional trial expands a patient’s own tumor-infiltrating lymphocytes, gene-edits them (GC203), and infuses them intravenously after non-myeloablative lymphodepletion with a single 600 mg dose of hydroxychloroquine and cyclophosphamide. TILs are manufactured from tumor tissue obtained at resection or biopsy and must be successfully produced prior to enrollment. The primary focus is safety and tolerability, with secondary measures of anti-tumor activity assessed by imaging and clinical outcomes. Participants are closely monitored for blood counts, organ function, and treatment-related adverse events during and after infusion.

Who should consider this trial

Good fit: Ideal candidates are adults 18–70 years old with histologically confirmed pancreatic ductal adenocarcinoma who have undergone tumor resection for GC203 TIL production, have ECOG 0–1, a life expectancy over 3 months, at least one evaluable lesion, adequate blood counts and organ function, and who have failed standard treatment regimens.

Not a fit: Patients with ECOG >1, very limited life expectancy, inadequate hematologic or organ function, inability to produce sufficient TILs from tumor tissue, or who have not yet tried standard therapies are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, GC203 TIL could provide a personalized immunotherapy option that shrinks tumors or extends survival for patients whose pancreatic cancer no longer responds to standard treatments.

How similar studies have performed: TIL therapy has produced durable remissions in melanoma and shown early promise in some other solid tumors, but gene-edited TIL approaches in pancreatic cancer are novel and remain largely unproven.

Eligibility criteria

Inclusion Criteria:

1. have done the tumor resection for gene-edited GC203 TIL production and successfully produced；
2. Age: 18 years to 70 years;
3. Histologically diagnosed as pancreatic ductal adenocarcinoma;
4. Expected life-span more than 3 months;
5. ECOG score 0-1;
6. Test subjects have failed standard treatment regimens, and be willing to recieve gene-edited GC203 TIL therapy;
7. At least 1 evaluable tumor lesion;
8. Hematology and Chemistry（within 7 days prior to enrollment）:

Absolute count of white blood cells≥2.5×10\^9/L; Absolute count of neutropils≥1.5×10\^9/L; Absolute count of lymphocytes ≥0.7×109/L； Platelet count≥90×10\^9； hemoglobin≥90 g/L; Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days); Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min; Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN); Totol bilirubin≤1.5×ULN; 9.Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent, and continue within 1 year after the completion of lymphodepletion； 10.Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy and biologics must cease 28 days before obtaining TILs; 12.Be able to understand and sign the informed consent document; 13.Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

1. with other malignant tumors,except for the malignancies that have been cured, have been inactive for ≥5 years prior to study inclusion and have a very low risk of recurrence; Non-melanoma skin cancer or malignant lentigo with adequate treatment and no evidence of disease recurrence; Carcinoma in situ with adequate treatment and no evidence of disease recurrence;
2. Need glucocorticoid treatment, and daily dose of Prednisone greater than 10mg(or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment;
3. Breathe indoor air in a quiet state, and the oxygen saturation of finger pulse is \< 95%;
4. Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive;
5. Significant cardiovascular anomalies according to any of the following definition:

   New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrio-ventricular conductive block, etc.
6. Uncontrolled metabolic disorders, such as diabetes, which is known to be uncontrolled, or other non-malignant organ or systemic disease or cancer secondary reactions, can lead to higher medical risk and/or uncertainty in the evaluation of survival;
7. Patients with esophageal or gastric varices requiring immediate intervention (e.g., ligation or sclerotherapy) or who, in the opinion of the investigator or in consultation with a gastroenterologist or hepatologist, have evidence of portal hypertension (including splenomegalgia on imaging) or a history of varicose bleeding must undergo endoscopic evaluation within the first 3 months of enrollment;
8. Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade B or more severe cirrhosis, liver failure;
9. Pulmonary fibrosis, interstitial lung disease (both past and present), acute lung disease;
10. Clinically uncontrollable third space effusion, such as pleural fluid and ascites that could not be controlled by drainage or other means prior to enrollment;
11. Patients with known pnelmeningeal metastases; Other patients known to have uncontrolled or untreated central nervous system metastases that are not effectively controlled by treatment, except those who have been treated and whose symptoms are stable, and who discontinue glucocorticoid and anticonvulsant therapy ≥4 weeks prior to cell retransfusion;
12. Severe physical or mental diseases;
13. Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection);
14. Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy;
15. History of allogeneic T cell therapy;
16. Having received immunotherapy and developed irAE level greater than Level 3;
17. Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded);
18. Females in pregnancy or lactation;
19. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
20. Researchers considering the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: boyong shen

Conditions Pancreatic Cancer; Pancratic Ductal Adenocarcinoma; Treatment Side Effects; Tumor Infiltrating Lymphocytes