IX001 TCR-T In the Treatment of Advanced Pancreatic Cancer and Colorectal Cancer Induced by KRAS Mutations

NCT06487377 | Recruiting Phase 1

• 1 other identifier: BT003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, single-center, open-label clinical study aimed at evaluating the safety and efficacy of IX001 TCR-T (T cell receptor-engineered T-Cell) injection in patients with advanced pancreatic cancer and colorectal cancer induced by KRAS (Kirsten Rat Sarcoma Viral Oncogene) mutations. A total of 6-18 evaluable patients are planned to be enrolled. The study will include 4 dose groups, using a '3+3' dose escalation design.

Conditions

Pancreatic Cancer; Colorectal Cancer

Keywords

KRAS-G12V or G12D

Outcome Measures

Primary Outcomes (3)

• Dose-limiting Toxicity (DLT)

  Proportion of patients with DLT

  4 weeks

• Adverse Events (AEs)

  Incidence and severity of adverse events

  96 weeks

• Serious Adverse Events (SAEs)

  Incidence and severity of serious adverse events

  96 weeks

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  12 weeks

• Disease Control Rate (DCR)

  12 weeks

• Changes in Serum Tumor Markers compared to Baseline

  12 weeks

• Duration of response (DOR)

  96 weeks

• Time to response (TTR)

  96 weeks

Study Arms (1)

IX001 TCR-T cells

EXPERIMENTAL

IX001 TCR-T cells targeted for KRAS mutation

Biological: IX001 TCR-T cells

Interventions

IX001 TCR-T cells BIOLOGICAL

IX001 TCR-T cell injection will be administered intravenously after lymphodepletion.

IX001 TCR-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:

• Voluntary signing of an informed consent form (ICF);
• Males or females, aged 18-70 years (inclusive);
• Pathologically diagnosed with advanced pancreatic cancer or colorectal cancer, having failed or intolerant to at least two lines of standard of care, including metastatic tumors (having received conventional chemotherapy), recurrent tumors (having undergone surgery and adjuvant chemotherapy in the past), or locally advanced tumors with disease progression after neoadjuvant treatment;
• At least one measurable lesion (according to RECIST1.1\[The Response Evaluation Criteria In Solid Tumors\] criteria);
• Patients with tumor tissue or peripheral blood testing positive for KRAS-G12V or G12D mutations and expression of matching HLA-A\*11, C\*01:02, or C\*08:02 subtypes;
• ECOG (Eastern Cooperative Oncology Group)≤2;
• Life expectancy ≥3 months;
• Absolute neutrophil count ≥1×10E9/L;
• Platelet count ≥50×10E9/L, hemoglobin\>90g/dL;
• Absolute lymphocyte count ≥0.5×10E9/L;
• Adequate functional reserve of organs:
• Aspartate aminotransferase ≤2.5×ULN (upper limit of normal);
• Aspartate transaminase ≤2.5×ULN;
• Creatinine clearance ≥60mL/min;
• Total serum bilirubin ≤1.5×UNL;

You may not qualify if:

• Other malignancies (except non-melanoma skin cancer with the disease-free survival of more than 5 years and cervical carcinoma in situ, bladder cancer, or breast cancer);
• A history of mental disorders, which may affect compliance with this protocol or lead to failure in signing the ICF;
• Poorly controlled hypertension with drug (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>90 mmHg) or occurrence of grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart diseases within one year prior to signing the ICF; QTc interval \>450 ms for males or QTc interval \>470 ms for females during screening (QTc interval calculated using the Fridericia formula);
• Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleural/peritoneal/pericardial catheter), except any dedicated central venous catheter;
• A history of or any central nervous system disorders, such as epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
• A positive result obtained in any of the following virological tests:
• Antibody to human immunodeficiency virus (HIV antibody);
• Hepatitis C virus antibody (HCV antibody), with a positive result for hepatitis C virus ribonucleic acid (HCV RNA);
• Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA) copies;
• Treponema pallidum antibody (TP antibody); patients may be enrolled after additional examinations are performed to exclude active syphilis where necessary;
• Fungal, bacterial, viral or other infections or suspected fungal, bacterial, viral or other infections that cannot be controlled or require intravenous administration;
• Significant tendency for bleeding, such as active gastrointestinal bleeding, coagulation disorders;
• Patients with a history of severe allergy or allergic constitution;
• A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus) requiring systemic immunosuppressive/systemic disease-modulating drugs in the past 2 years;
• Interstitial lung disease (such as pneumonia, pulmonary fibrosis), or a history of clinically significant respiratory system diseases during screening;

Sponsors & Collaborators

• Shanghai Pudong Hospital: lead
• ImmuXell Biotech Ltd.: collaborator

Study Sites (1)

Shanghai Pudong Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• MingHua Yu, Dr.

  Shanghai Pudong Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MingHua Yu, Dr.

CONTACT

18017821601; minghua_md@fudan.edu.cn

ZhiGuo Long, M.D.

CONTACT

18117253161; zglong1976@126.com

Study Design

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

Model Details: 3+3 dose escalation

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: July 5, 2024
• Study Start: July 1, 2024
• Primary Completion: March 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 5, 2024

Record last verified: 2024-07

Locations

CN (1)