A Open, Single Arm, Phase IIa Clinical Study on the Safety, Pharmacokinetics, and Efficacy of ScTIL (Genetically Modified Tumor Infiltrating Lymphocytes) in the Treatment of Gynecological Malignancies

Peking Union Medical College Hospital0 sites30 target enrollmentApril 18, 2022

Overview

Brief Summary

The purpose of this study is to evaluate the safety and clinical efficacy of ScTIL in the treatment of recurrent or refractory cervical cancer, ovarian cancer and malignant trophoblastic tumor, to evaluate the pharmacokinetic characteristics of ScTIL, and to explore and analyze the changes of CTC, ctDNA and immunohistochemical Library of malignant tumor subjects before and after ScTIL treatment.Treatment will be terminated upon progressive disease, unacceptable toxicity, or withdrawal of consent. Subjects with responses other than progressive disease will receive subsequent rounds of ScTIL treatment.

Detailed Description

The purpose of this study is to evaluate the safety and clinical efficacy of ScTIL in the treatment of recurrent or refractory cervical cancer, ovarian cancer and malignant trophoblastic tumor, to evaluate the pharmacokinetic characteristics of ScTIL, and to explore and analyze the changes of CTC, ctDNA and immunohistochemical Library of malignant tumor subjects before and after ScTIL treatment. Treatment will be terminated upon progressive disease, unacceptable toxicity, or withdrawal of consent. Subjects with responses other than progressive disease will receive subsequent rounds of ScTIL treatment. The primary endpoint was objective response rate, defined as the proportion of patients with complete or partial response. Secondary endpoints were duration of response (time from the first evidence of response to disease progression or death, whichever came first), progression-free survival (time from the treatment initiation to disease progression or death, whichever came first), overall survival (time from the treatment initiation to the date of death or end of follow-up).

Registry

clinicaltrials.gov

Start Date

April 18, 2022

End Date

May 31, 2024

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Peking Union Medical College Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 18 and ≤ 75, female;
•Expected survival time \> 3 months;
•Clinically diagnosed advanced gynecological tumors, including:
•cervical cancer;
•Ovarian cancer;
•Malignant trophoblastic tumor;
•Patients who have received radical surgery ± adjuvant radiotherapy and chemotherapy, or who have disease progression or recurrence after receiving too many lines of radiotherapy and chemotherapy, who have been unable to be resected again or who cannot tolerate radiotherapy and chemotherapy;
•Patients with cervical and ovarian cancer have at least one measurable lesion according to RECIST version 1.1 standard; Patients with malignant trophoblastic tumor β HCG ≥ 5, with or without measurable lesions.
•Voluntarily accept peripheral blood apheresis ± surgical resection of fresh tumor tissue to obtain cells for cell preparation, and the proportion of peripheral blood PD-1 positive T cells in the total T cells is ≥ 18%. For patients who have received PD-1 monoclonal antibody treatment before screening, the proportion of peripheral blood PD1 positive T cells in the total T cells is ≥ 10%;
•The ECOG physical condition score is 0 to 1;

Exclusion Criteria

•Central nervous system metastasis or meningeal metastasis with clinical symptoms, or there is other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, which is not suitable for inclusion according to the judgment of the researcher;
•Subjects with a history of second malignancy within 5 years before signing the informed consent;
•Patients who had previously received PD-L1 mAb;
•Those who have active infection within 1 week before apheresis and currently need systematic anti infection treatment;
•Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before apheresis, Except for the following:
•Nitrosourea or mitomycin C were within 6 weeks before single harvest;
•Oral fluorouracils and small molecule targeted drugs were taken 1 week before apheresis.
•Within 2 weeks before apheresis:
•Have received systemic glucocorticoid (prednisone \> 10mg/day or equivalent dose of similar drugs) or other immunosuppressant treatment; Except for the following cases: local, eye, intra-articular, intranasal and inhaled glucocorticoids; Short term use of glucocorticoids for preventive treatment (e.g. prevention of contrast agent allergy);
•Used immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc;

Arms & Interventions

Cohort 1

Study subjects: Patient with cervical carcinoma

Intervention: Toripalimab + ScTIL

Cohort 2

Study subjects: Patient with ovarian cancer

Intervention: Toripalimab + ScTIL

Cohort 3

Study subjects: Patient with malignant trophoblastic tumor

Intervention: Toripalimab + ScTIL

Outcomes

Primary Outcomes

Objective response rate

Time Frame: 12 weeks

The proportion of patients with complete or partial response of cervical and ovarian cancer according to RECIST version 1.1, malignant trophoblastic tumor according to serum hCG level. Complete response was defined as a normal hCG level measured for 3 consecutive weeks. Partial response was defined as a ≥50% decrease in hCG level from baseline after 2 cycles.