Evaluate the Safety and Efficacy of BGT007H Cell Therapy in Patients With Relapsed/Refractory Pancreatic Cancer

Clinical Study on the Safety and Preliminary Efficacy of BGT007H Cell Therapy in Patients With Recurrent/Refractory Pancreatic Cancer

The primary objective of this study is to evaluate the safety and tolerability of BGT007H cell therapy in patients with recurrent/refractory pancreatic cancer.

Study Overview

• Status: Recruiting
• Conditions: Tumor Pancreas
• Intervention / Treatment: Drug: BGT007H Cell Injection

Detailed Description

This study is a single-arm, open-label, modified "3+3" dose-escalation exploratory study. The BGT007H cell therapy group will be evaluated at 5 dose levels, which are (3.0×10^7, 1.0×10^8, 2.0×10^8, 3.0×10^8, 4.0×10^8) BGT007H cells. If a lower adverse reaction and preliminary benefit (SD or PR) are observed, the same dose will be repeated 1-2 times after a 1-month interval.

Each subject will be observed for at least 4 weeks after cell infusion (DLT observation period). The first two dose groups (3.0×10^7, 1.0×10^8 cells) will each include 1 subject, and the remaining 3 dose groups will follow the conventional "3+3" dose-escalation method. If a DLT occurs in the first subject at the first dose level, an additional 5 subjects will be included. If no DLT occurs in the expanded subjects, the study will proceed to the next higher dose group. If another subject experiences a DLT, enrollment will be halted and the study protocol will be revised. The next subject can only be enrolled if it is confirmed that the previous subject did not experience grade 3 or higher adverse events related to the study drug (CTCAE 5.0) during the DLT observation period. If no DLT occurs in a dose group, the study will proceed to the next higher dose group. In a group of 3 subjects, if one experiences a DLT, an additional 3 subjects will be included in the next higher dose group. If one out of three subjects experiences a DLT, 3 more subjects will be included in the dose group. If only one out of the expanded 6 subjects experiences a DLT, then the study will proceed to include 3 more subjects at the next higher dose. If 2 or more out of the expanded 6 subjects experience a DLT, then the dose is considered to be higher than the MTD (MTD is defined as the highest dose at which ≤1/6 or ≤2/9 subjects experience a DLT). New subjects will be enrolled at the previous lower dose (tolerated dose) group until 6 or 9 subjects are reached in the lower dose group. If ≤1/6 or ≤2/9 subjects, this lower dose group is defined as the MTD or the optimal effective dose. During the study, the investigators may consider the safety and preliminary efficacy data of the enrolled subjects, with the safety of the subjects and the maximum benefit of the disease as the premise, and conduct the study treatment at the maximum tolerated dose or other doses determined by the investigators.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiuqi Wu, Doctorate; Phone Number: 15850459057; Email: wuxiuqi597@163.com
• Study Contact Backup: Name: Jiujie Cui, Doctorate; Phone Number: 13621958524; Email: cuijiujie@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Renji Hospital
      • Contact: Liwei Wang, Dr; Phone Number: +86 16621086648; Email: lwwang2013@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. voluntarily sign an informed consent form in writing.
2. Age ≥18 years and ≤75 years, both male and female are eligible.
3. Expected survival ≥ 3 months.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
5. Can provide pathological paraffin section detection targets (within 3 years prior to signing the informed consent form).
6. According to the RECIST v1.1 criteria for the evaluation of solid tumors, there must be at least one measurable lesion, and the longest diameter of the lesions assessed by CT or MRI at baseline must be ≥ 10 mm (excluding lymph nodes, for which the short diameter must be ≥ 15 mm).
7. Advanced pancreatic cancer confirmed by histology or cytology, with progression after second-line or later standard treatment, or intolerance to standard treatment, or no standard treatment available. The definition of intolerance: according to CTCAE v5.0, grade ≥IV hematological toxicity or grade ≥III non-hematological toxicity or grade ≥II damage to major organs such as heart, liver, and kidney occurred during treatment. The definition of treatment failure: disease progression (PD) during treatment or recurrence after treatment (including postoperative recurrence).
8. Apheresis or venous blood collection venous access can be established, and there are no other contraindications to blood cell separation.
9. Has adequate organ and bone marrow function, defined as follows: Blood routine: Neutrophil count (NEUT#) ≥1.0×10^9/L Platelet count (PLT) ≥70×10^9/L Hemoglobin concentration ≥80g/L Liver function: For subjects without liver metastasis: Aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤2.5× ULN Total bilirubin (TBIL) ≤1.5× ULN For subjects with liver metastasis: AST ≤5× ULN ALT ≤5× ULN For subjects with liver metastasis or Gilbert's syndrome: Total bilirubin (TBIL) ≤2.5× ULN Renal function: Creatinine clearance rate (CCR) ≥50 mL/min Coagulation function: International normalized ratio (INR) ≤1.5× ULN Activated partial thromboplastin time (APTT) ≤1.5× ULN Coagulation function in subjects with liver metastasis: INR ≤2× ULN APTT ≤2× ULN.
10. During the study period and within 6 months after the end of dosing, subjects with childbearing potential (both male and female) must use effective medical contraception measures. Female subjects of childbearing potential must undergo a pregnancy test within 72 hours before the first dosing, and the result must be negative.

Exclusion Criteria:

1. Has active central nervous system (CNS) metastasis (except for those treated and stable).
2. HIV positive, HBsAg positive with positive Hepatitis B virus (HBV) DNA copy number (greater than the lower limit of detection), Hepatitis C virus (HCV) antibody positive and HCV RNA positive, syphilis non-treponemal antibody (RPR or TRUST) positive.
3. Has a mental or psychological disorder that cannot cooperate with treatment and efficacy evaluation.
4. Subjects with severe autoimmune diseases who have been long-term users of immunosuppressants.
5. Within 14 days before enrollment, there is an active infection or uncontrollable infection that requires systemic treatment.
6. Any unstable systemic diseases (including but not limited to): active infection (except for localized infection); unstable angina; cerebral ischemia or cerebral stroke (within 6 months of screening); myocardial infarction (within 6 months of screening); congestive heart failure (New York Heart Association (NYHA) class ≥ III); severe arrhythmia requiring medication treatment; heart disease requiring treatment or uncontrolled hypertension after treatment (blood pressure > 160 mmHg/100 mmHg).
7. Combined with dysfunction of important organs such as lungs, brain, and kidneys.
8. Within 4 weeks before receiving cell therapy, the subject has undergone major surgery or serious trauma, or is expected to undergo major surgery during the study period.
9. Within 1-2 weeks or 5 half-lives (whichever is shorter) before apheresis, the subject has received any systemic chemotherapy, immunotherapy, or small molecule targeted therapy.
10. Received chimeric antigen receptor-modified T cell (CAR-T), T-cell receptor engineered T cells (TCR-T) therapy within the past 6 months.
11. Severe allergies or a history of allergies.
12. Subjects who require anticoagulant therapy.
13. Pregnant or lactating women, or those who plan to become pregnant within six months (applicable to both men and women).
14. The researcher believes that there are other reasons why the subject cannot be included in the treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BGT007H Cell Injection; A modified "3+3" dose-escalation design is used, with BGT007H cells administered at five progressively increasing dose levels for treatment evaluation. The dose levels are (3.0×10^7, 1.0×10^8, 2.0×10^8, 3.0×10^8, 4.0×10^8) BGT007H cells.

Drug: BGT007H Cell Injection; Intervention roughly goes through 3 phases (the day of cell infusion is defined as day 0, d0): Apheresis and baseline period: Eligible subjects are enrolled for leukapheresis to prepare BGT007H cell injection solution, and baseline assessment is performed from after apheresis to before preconditioning.; Preconditioning (d-5~d-3): Patients begin preconditioning (FC regimen) 5 days before BGT007H cell administration. A 2-day rest and observation period is conducted after preconditioning.The FC regimen is as follows:Fludarabine: 25~30mg/m2/d, intravenous infusion, once a day, for 3 consecutive days;Cyclophosphamide: 250~350mg/m2/d, intravenous infusion, once a day, for 3 consecutive days.; Cell infusion (d0) and DLT observation period (d0~d28).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicity (DLT)	Dose-Limiting Toxicity	through study completion, an average of 3 year
Maximum Tolerated Dose (MTD)	Maximum Tolerated Dose	through study completion, an average of 3 year
Optimal Biological Dose (OBD)	Optimal Biological Dose	through study completion, an average of 3 year
Adverse events (AE)	Adverse events	through study completion, an average of 3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the disease control rate (DCR)	Evaluate the disease control rate ,according to the RECIST 1.1 criteria.	through study completion, an average of 3 year
Evaluate the duration of response (DOR)	Evaluate the duration of response ,according to the RECIST 1.1 criteria.	through study completion, an average of 3 year
Evaluate the progression-free survival (PFS)	Evaluate the progression-free survival, according to the RECIST 1.1 criteria.	through study completion, an average of 3 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the overall survival (OS)	Evaluate the overall survival ,according to the RECIST 1.1 criteria.	through study completion, an average of 3 year

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Liwei Wang, Doctorate, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2024
• Last Update Submitted That Met QC Criteria: June 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: BR-BGT-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No