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L-TIL Plus Tislelizumab for PD1 Antibody Resistant aNSCLC

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
L-TIL, Tislelizumab, Docetaxel
Sponsored by
Quanli Gao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring L-TIL, PD1 antibody resistance, Tislizumab, Chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. Non-small cell lung cancer patients diagnosed by pathological histology. 2. Imaging examination showed stage IV disease. 3. Non-squamous cancer patients shall be EGFR , ALK, ROS1, RET, MET negative. 5. Failure from PD-1 antibodies treatment, including treatment ineffective or effective for a period then progress. 6. The Eastern Oncology Collaboration Group (ECOG) scores 0-1. 7. At least one imaging lesion can be measured, according to the standard for evaluating the effectiveness of solid tumors (RECIST 1.1). 8. Asymptomatic or stable symptoms after local treatment is allowed. 9. Subjects are allowed to receive palliative radiation. 10. Enough organ functions well. 11. Patients have good superficial venous blood circulation, which can meet the needs of intravenous dripping. 12. No other serious diseases that conflict with this study regimes (e.g. autoimmune diseases, immune deficiencies, organ transplants, chronic infections). 13. For female subjects with reproductive age, the pregnancy test should be accepted within 3 days prior to the first study drug administered (day 1 of cycle 1) and the results are negative. 14. In the event of a risk of conceival, all subjects (male or female) must adopt contraception at a rate of less than 1% annually for the entire treatment period up to 120 days after the last study of the drug was administered (or 180 days after the last study of the drug). 15. The patient himself agrees to participate in this clinical trial, sign the Informed Consent Letter, complete the procedure, treatment, and follow-up. Exclusion Criteria: Small cell lung cancer (SCLC), including mixing pathology, combined with SCLC and NSCLC. Accepted radiation treatment in special organ before the first drug was administered, eg: more than 30% bone marrow within 14 days. Diagnosed with second malignant diseases within five years. Participating in other clinical trial. Treatment with other drugs, including thymus peptide, interferon, interleukin, and so on. Active autoimmune diseases requires systemic treatment. Receiving glucocorticoid therapy, excluding local glucocorticoids in nose, inhalation or other pathways, or any other form of immunosuppressive therapy. Uncontrolled chest and abdominal fluid. Patients have accepted organ transplantation or hematopoietic stem cell transplantation. Allergic to intervention drugs, including ingredients and auxiliary components. 11. Incomplete recovery from the adverse events. 12. Active hepatitis B or HCV infection. 13. Accepted active vaccines within 30 days before the first dose. 14. Women who are pregnant or breastfeeding. 15. Symptomatic CNS metastasis. 16. Uncontrolled active infections, eg. sepsis, mycemia, fungal hematoma. 17. With serious mental disorders. 18. Other conditions that the researchers believe in having potential risks which are not suitable for this study.

Sites / Locations

  • No.127 Dongming RoadRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

L-TIL plus Tislelizumab and Docetaxel

Arm Description

Tislelizumab, 200mg, ivgtt, d1, Q3W for one year L-TIL cells, (3-10)x10^9/m2, ivgtt, d14, Q3W for 4 or 6 cycles Docetacel, 75mg/m2, ivgtt, d1, Q3W for 4 cycles

Outcomes

Primary Outcome Measures

ORR
overall response rate (including complete response and partial response)

Secondary Outcome Measures

PFS
duration of disease stable or better
DCR
disease control rate (including patients who achieved complete response, partial response and stable disease)
DOR
duration of response

Full Information

First Posted
May 6, 2023
Last Updated
May 17, 2023
Sponsor
Quanli Gao
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1. Study Identification

Unique Protocol Identification Number
NCT05878028
Brief Title
L-TIL Plus Tislelizumab for PD1 Antibody Resistant aNSCLC
Official Title
L-TIL Plus Tislelizumab as Second Line Therapy for PD-1 Inhibitor Resistant Advanced NSCLC Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 16, 2022 (Actual)
Primary Completion Date
September 15, 2023 (Anticipated)
Study Completion Date
September 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Quanli Gao

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this observational study is to test in advanced non-small cell lung cancer patients with negative driver gene. For these patients, PD1 antibody therapy combined with chemotherapy was the preferred regimen. However, there is no standard regimen for the patients who refractory from the first-line PD1 inhibitor based therapy. The main questions they aim to answer are: 1.The efficacy of Liquid Tumor Infiltrating Lymphocytes (L-TIL) plus Tislelizumab and Docetaxel for patients failure from first line chemotherapy and PD1 inhibitor therapy. 2. The safety of L-TIL plus Tislelizumab and Docetaxel as second line therapy. All participants will receive four cycles of Docetaxel chemotherapy, six cycles of L-TIL cells infusion and one year of Tislelizumab treatment except for disease progression, intolerable toxicity, withdrawal informed consent, death and so on.
Detailed Description
This study is one arm, single center, phase II clinical trial. The participants were diagnosed with metastatic non-small cell lung cancer but without actionable biomarkers (eg: EGFR, ALK, MET, ROS1). PD1 inhibitor and chemotherapy as first line therapy was not respond, or develop tumor progression after a response. Four cycles of Docetaxel chemotherapy, six cycles of L-TIL cells infusion and one year of Tislelizumab regimen Q3W were used. Docetacxel was dosed 75mg/m2 and Tislelizumab was dosed 200mg on day 1, L-TIL cells were dosed (3-10)x10*9/m2 on day 14. Eligible patients were no less than 18 and no more than 75 years old, with adequate organ function but without active infection and autoimmune disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
L-TIL, PD1 antibody resistance, Tislizumab, Chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-TIL plus Tislelizumab and Docetaxel
Arm Type
Experimental
Arm Description
Tislelizumab, 200mg, ivgtt, d1, Q3W for one year L-TIL cells, (3-10)x10^9/m2, ivgtt, d14, Q3W for 4 or 6 cycles Docetacel, 75mg/m2, ivgtt, d1, Q3W for 4 cycles
Intervention Type
Combination Product
Intervention Name(s)
L-TIL, Tislelizumab, Docetaxel
Other Intervention Name(s)
Liquid Tumor Infiltrating Lymphocytes
Intervention Description
PD1 positive lymphocytes were collect, isolated, and expanded from peripheral blood, then infused back into the patient's body. Besides this, Tislelizumab and Docetaxel were used as combination therapy.
Primary Outcome Measure Information:
Title
ORR
Description
overall response rate (including complete response and partial response)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
PFS
Description
duration of disease stable or better
Time Frame
6 months and 12 months
Title
DCR
Description
disease control rate (including patients who achieved complete response, partial response and stable disease)
Time Frame
3 months
Title
DOR
Description
duration of response
Time Frame
6 months and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Non-small cell lung cancer patients diagnosed by pathological histology. 2. Imaging examination showed stage IV disease. 3. Non-squamous cancer patients shall be EGFR , ALK, ROS1, RET, MET negative. 5. Failure from PD-1 antibodies treatment, including treatment ineffective or effective for a period then progress. 6. The Eastern Oncology Collaboration Group (ECOG) scores 0-1. 7. At least one imaging lesion can be measured, according to the standard for evaluating the effectiveness of solid tumors (RECIST 1.1). 8. Asymptomatic or stable symptoms after local treatment is allowed. 9. Subjects are allowed to receive palliative radiation. 10. Enough organ functions well. 11. Patients have good superficial venous blood circulation, which can meet the needs of intravenous dripping. 12. No other serious diseases that conflict with this study regimes (e.g. autoimmune diseases, immune deficiencies, organ transplants, chronic infections). 13. For female subjects with reproductive age, the pregnancy test should be accepted within 3 days prior to the first study drug administered (day 1 of cycle 1) and the results are negative. 14. In the event of a risk of conceival, all subjects (male or female) must adopt contraception at a rate of less than 1% annually for the entire treatment period up to 120 days after the last study of the drug was administered (or 180 days after the last study of the drug). 15. The patient himself agrees to participate in this clinical trial, sign the Informed Consent Letter, complete the procedure, treatment, and follow-up. Exclusion Criteria: Small cell lung cancer (SCLC), including mixing pathology, combined with SCLC and NSCLC. Accepted radiation treatment in special organ before the first drug was administered, eg: more than 30% bone marrow within 14 days. Diagnosed with second malignant diseases within five years. Participating in other clinical trial. Treatment with other drugs, including thymus peptide, interferon, interleukin, and so on. Active autoimmune diseases requires systemic treatment. Receiving glucocorticoid therapy, excluding local glucocorticoids in nose, inhalation or other pathways, or any other form of immunosuppressive therapy. Uncontrolled chest and abdominal fluid. Patients have accepted organ transplantation or hematopoietic stem cell transplantation. Allergic to intervention drugs, including ingredients and auxiliary components. 11. Incomplete recovery from the adverse events. 12. Active hepatitis B or HCV infection. 13. Accepted active vaccines within 30 days before the first dose. 14. Women who are pregnant or breastfeeding. 15. Symptomatic CNS metastasis. 16. Uncontrolled active infections, eg. sepsis, mycemia, fungal hematoma. 17. With serious mental disorders. 18. Other conditions that the researchers believe in having potential risks which are not suitable for this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Quanli NA Gao, PhD
Phone
86-0371-65587951
Email
zlyygql@zzu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaomin NA Fu, PhD
Phone
86-0371-65587483
Email
fuxiaomin0880@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YanYan NA Liu, phD
Organizational Affiliation
Henan Cancer Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
No.127 Dongming Road
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaomin NA Fu, PhD
Phone
86-0371-65587187
Email
fuxiaomin0880@126.com

12. IPD Sharing Statement

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L-TIL Plus Tislelizumab for PD1 Antibody Resistant aNSCLC

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