TIL for Patients With Advanced Solid Tumor

Tumor Infiltrating Lymphocyte (TIL) Therapy for the Treatment of Advanced Solid Tumors

Background:

Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to patients.

TIL therapy has shown strong efficacy for the treatment of solid tumors and has achieved high objective response rates in multiple cancers, such as melanoma, NSCLC, and cervical cancer.

Objective:

To evaluate the safety and efficacy of TIL for the patients with advanced solid tumor.

Eligibility:

Adults aging 18-75 with advanced solid tumor.

Design:

1. Patients will undergo screening tests, including imaging procedures, heart and lung tests, and lab tests.
2. Freshly resected patient tumors were dissected by the surgeon.
3. TIL cells were isolated from the patient's tumor tissue, then cultured in vitro, activated and expanded.
4. At last TIL cells will be re-infused into the patients.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: Autologous tumor-infiltrating lymphocyte cells

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tangfeng Lv, PhD; Phone Number: +86 25 8086 0114; Email: bairoushui@163.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
      • Contact: Xiugui Sheng, PhD; Email: hanxiuchen@yeah.net
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Nanjing Jinling Hospital
      • Contact: Tangfeng Lv, PhD; Phone Number: +86 25 8086 0114; Email: bairoushui@163.com
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Wowen's hospital, School of medicine, Zhejiang University
      • Contact: Hui Wang, PhD; Email: 5198008@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial.
2. Age ≥ 18 years and ≤ 75 years.
3. Expected survival time > 3 months.
4. ECOG score 0-1.
5. At least one lesion that could undergo surgery or biopsy to obtain tumor tissue for TIL preparation.
6. At least 1 measurable lesion (according to RECIST v1.1).
7. Metastatic or recurrent solid tumor, confirmed by histopathology. Patients who have failed previous standard treatment or currently do not have standard treatment, or who have been determined by the researcher to be unsuitable for current standard treatment due to other reasons.
8. Any previous anti-tumor treatment must exceed 28 days when collecting tumor tissue; The tumor tissue used for collecting and preparing TIL should not have undergone local treatment.

9. The bone marrow function of the subject's meets the following requirements:

   1. Absolute neutrophil count (ANC) ≥ 1.5× 10e9/L.
   2. Platelet (PLT） ≥ 75× 10e9/L.
   3. Hemoglobin (HGB) ≥ 90 g/L.

10. Liver and kidney function:

    1. Serum creatinine (Cr) ≤ 1.5 times of upper limit of normal (ULN) or creatine clearance ≥ 60 ml/min.
    2. Serum Alanine aminotransferase (ALT) or/and Aspartate aminotransferase (AST) ≤ 2.5 times of ULN.
    3. Total bilirubin (TBIL) ≤ 1.5 times of ULN.

11. Blood coagulation function:

    1. Prothrombin time (PT) ≤ 1.5 ULN.
    2. International Normalized Ratio (INR) ≤ 1.5 ULN.
    3. or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 ULN.
12. Left Ventricular Ejection Fractions (LVEF）≥45%.
13. Forced Expiratory Volume in the first second (FEV1）≥50%.
14. Women or men of childbearing potential should be ascetic or take contraception since the signing of ICF to 24 weeks or later after the last administration of drug.

Exclusion criteria:

1. Female subjects who are in pregnancy or lactation or have a positive baseline blood pregnancy test.
2. Individuals who have experienced severe allergic reactions to any drug or its components in this trial in the past.
3. Received any investigational medication within 28 days prior to TIL cell transfusion or participated in another clinical study at the same time.
4. History of other known malignant tumors within the previous 5 years.
5. Primary central nerve system (CNS) cancer, or Participants with CNS metastasis after localized treatment.
6. History or syndrome of autoimmune diseases.
7. History of immunodeficiency, including testing positive for Human Immunodeficiency Virus (HIV), or having other acquired or congenital immunodeficiency diseases.
8. Have a history of ≥ grade 3 thromboembolic events within the past 6 months or are currently receiving thrombolytic or anticoagulant treatment due to high risk of thrombosis.
9. History of hereditary or acquired hemorrhagic diseases.
10. Clinical cardiovascular diseases or symptoms.
11. Active infection present.
12. Active pulmonary tuberculosis infection.
13. positive hepatitis B surface antigen or positive hepatitis B core antibody or positive hepatitis C virus antibody.
14. Syphilis spirochete antibody positive.
15. Patients received major surgery or under severe injury within 28 days before TIL infusion.
16. Patients who received live vaccine or attenuated live vaccine 28 days before TIL infusion.
17. Patients who have drug addiction history, alcoholism, or drug users.
18. Patients who have previously received cell therapy (such as TCR-T, CAR-T, TIL, etc.)
19. Patients not suitable for the clinical trial evaluated by the investigators.

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: TILs; Biological: TILs Drug: IL-2	Biological: Autologous tumor-infiltrating lymphocyte cells; On day 0, all patients will receive autologous tumor-infiltrating lymphocyte cells administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of TIL	The safety of TIL will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase.	Day 0 - Day 730

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	To evaluate the proportion of participants who have a confirmed partial response (PR) and complete response (CR) per RECIST v1.1 and iRECIST as assessed by the investigator.	Day 0 - Day 730
Duration of Response (DOR)	To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 and iRECIST as assessed by the investigator until disease progression or death due to any cause.	Day 0 - Day 730
Disease Control Rate (DCR)	To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) per RECIST v1.1 and iRECIST as assessed by the investigator.	Day 0 - Day 730
Progression free survival (PFS)	To evaluate the time from the date of TIL infusion until disease progression per RECIST v1.1 and iRECIST as assessed by the investigator or death due to any cause.	Day 0 - Day 730
Overall survival (OS)	To evaluate the time from the date of TIL infusion to death due to any cause.	Day 0 - Day 730

Collaborators and Investigators

• Sponsor: Hervor Therapeutics
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Women's Hospital School Of Medicine Zhejiang University; Jinling Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HV-IIT

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