Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 1 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 2 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 4 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

To deplete Tregs before collecting peripheral blood

Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

PD-1 Knockout T Cells

You Lu, MD

This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic non-small cell lung cancer. Blood samples will also be collected for research purposes.

This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.

PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer

A Phase I Clinical Trial of PD-1 Knockout Engineered T Cells Treating Patients With Advanced Non-small Cell Lung Cancer

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."

Response will be evaluated according to RECIST v1.1 for target lesions at Week 8：Complete Response (CR), Disappearance of all extranodal target lesions; Partial Response (PR) ≥ 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Disease control = CR +PR+SD

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

OS is defined as the time interval from date of first edited T cell infusion to the date of death due to any reason

Driver genes mutaion stauts of Participants in ctDNA from peripheral blood were assessed by next generation sequencing (NGS), to explore the positive rate of sepicif driver genes (e.g. EGFR, ALK, ROS1, etc.) and the relationship between gene mutation status and clinical response

Peripheral Interleukin-6 level at different timepoint (Baseline, 1 month and 3 month) was measured using rate nephelometry

Peripheral Interleukin-10 level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.

Peripheral Tumor Necrosis Factor-a level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.

Chengdu MedGenCell, Co., Ltd.

Sichuan University

Chair of Department of Thoracic Cancer

Grade 1/2 treatment-related adverse events (AEs) occurred in 11 of the 12 patients and There were no grade ≥3 treatment-related AEs

Grade 1/2 treatment-related adverse events (AEs) occurred in 2 patients.

Pre-A Cohort

Grade 1/2 treatment-related adverse events (AEs) occurred in 4 patients.

A Cohort

Grade 1/2 treatment-related adverse events (AEs) occurred in 3 patients.

B Cohort

C Cohort

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 2 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of one cycle of treatment.

Cyclophosphamide: To deplete Tregs before collecting peripheral blood

PD-1 Knockout T Cells: Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

Pre-A-One Cycle

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 1 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

Cyclophosphamide: To deplete Tregs before collecting peripheral blood

PD-1 Knockout T Cells: Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

A - Two Cycles

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 2 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

Cyclophosphamide: To deplete Tregs before collecting peripheral blood

PD-1 Knockout T Cells: Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

B- Two Cycles

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 4 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

Cyclophosphamide: To deplete Tregs before collecting peripheral blood

PD-1 Knockout T Cells: Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

C- Two Cycles

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

China

Region of Enrollment

You Lu

Number of Participants With Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of Dose of PD-1 Knockout T Cells Using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in Patients

In Pre-A Cohort, all patient were assessed per RECIST v1.1

In A Cohort, 3 patients were assessed per RECIST v1.1. One patient was unavailable for tumor response assessment due to early withdrawal.

In B Cohort, all patients were assessed per RECIST v1.1.

In C Cohort, all patients were assessed per RECIST v1.1.

Number of Patients With Overall Response

In Pre-A Cohort, all two patients were assessed per RECIST v1.1.

3 patients were assessed per RECIST v1.1. One patient was unavailable for tumor response assessment due to early withdrawal.

All patients were assessed per RECIST v1.1.

Number of Patients With Disease Control at 8 Weeks

Progression Free Survival (PFS)

In Pre-A Cohort, two patients were followed up.

In B Cohort, all patients were followed up.

Overall Survival (OS)

All patients were tested for gene mutation status in ctDNA at baseline

Only three patients were detected with EGFR mutations. Correlation between driver gene mutations with clinical outcome were not analyzed due to limited data. EGFR positive rate was showed in outcome measure data table.

Number of Participants With Genes Mutations in Peripheral Blood Circulating Tumor DNA (ctDNA)

baseline

1 month

3 month

In Pre-A Cohort, one patient provided blood smaple at baseline, month 1 and month 3, the other patient provided blood sample only at baseline and month 1.

Three patients were collected blood at baseline and month 1. The other patient's sample was not collected owing to early withdrawal from the trial. All patients had relapsed disease before month 3 and were not able to samples at month 3.

In B Cohort, One patient's blood was collected at baseline, month 1 and month 3. The other two patients' sample were collected only at baseline and month 1 owing to PD before month 3.

In C Cohort, One patient's blood was collected blood at baseline, month 1 and month 3. The other two patients' blood were only collected blood at baseline and month 1, owing to PD before month 3.

One patients did not provide blood sample due to early withdrawal; blood samples of 8 patients were only collected at baseline and month 1 due to PD before month 3

Interleukin-6 Change in the Peripheral Blood.

In Pre-A Cohort, one patient's blood was collected blood at baseline, month 1 and month 3, the other patient's blood was collected at baseline and month 1.

Three patients' samples were collected at baseline and month 1. The other patient's sample was not collected owing to early withdrawal from the trial. All patients had relapsed disease before month 3 and did not provide samples at month 3

In B Cohort, One patient's sample was collected at baseline, month 1 and month 3. The other two patients' samples were collected only at baseline and month 1, owing to PD before month 3.

In C Cohort, one patient's sample was collected at baseline, month 1 and month 3. The other two patients' samples were collected only at baseline and month 1, owing to PD before month 3.

Interleukin-10 Change in the Peripheral Blood.

In Pre-A Cohort, one patient's blood was collected at baseline, month 1 and month 3, the other patient's blood was collected only at baseline and month 1.

Three patients provided blood samples at baseline and month 1. The other patient's sample was not collected owing to early withdrawal from the trial. All patients had relapsed disease before month 3 and were not able to provide samples at month 3

In B Cohort, one patient's sample was collected at baseline, month 1 and month 3. The other two patients' sample were collected only at baseline, month 1 owing to PD before month 3.

In C Cohort, one patient's sample was collected at baseline, month 1 and month 3. The other two patients' sample were collected only at baseline, month 1 owing to PD before month 3.

Tumor Necrosis Factor-a Change in the Peripheral Blood.

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

A total of 2 x 10\^7/kg PD-1 Knockout T cells will be infused in one cycle which is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of one cycle of treatment.

Cyclophosphamide: To deplete Tregs before collecting peripheral blood

PD-1 Knockout T Cells: Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

Spots Global Cancer Trial Database for PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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