TAEST16001 in the Treatment of Soft Tissue Sarcoma

NCT04318964 | Unknown Phase 1

• 1 other identifier: SunYat-senU-TAEST16001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open, single arm, dose increasing early clinical study, which is divided into two parts: "3 + 3" designed dose escalation study and extended group study. The purpose of this study is to evaluate the safety, tolerance, PK, PD characteristics, and preliminary efficacy of TAEST16001 immunotherapy in the treatment of patients with solid tumor maily containing soft tissue sarcoma whose tumor antigen NY-ESO-1 expression is positive (HLA-A \* 02:01).

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerable dose (MTD）

  MTD was defined as the previous lower dose of DLT in ≥ 2 / 6 patients.

  Time Frame: From cell infusion up to 28 days

• Dose limited toxicity (DLT)

  Adverse events associated with cell therapy are identified by the safety review board (SRC)

  Time Frame: From cell infusion up to 28 days

Secondary Outcomes (9)

• Peripheral blood TAEST16001 cell peak (C Max)

  From cell infusion up to 28 days

• Peripheral blood TAEST16001 cell peak time (T Max)

  From cell infusion up to 28 days

• Peripheral blood TAEST16001 cell AUC 0-28

  From cell infusion up to 28 days

• T cell subsets

  From cell infusion up to 28 days

• Peripheral blood antigen-specific CTL

  From cell infusion up to 28 days

Study Arms (1)

TAEST16001 cells treat tumor antigen NY-ESO-1

EXPERIMENTAL

The dose escalation was carried out according to the principle of "3 + 3" increase. Four dose levels (calculated by the number of tcr-t positive cells) were set up: the dose level was 1: 5 × 108 ± 30%; the dose level was 2: 2 × 109 ± 30%; the dose level was 3: 5 × 109 ± 30%; the dose level was 4: 1.2 × 1010 ± 30%. Three patients in the first group, if there is no DLT, they will be enrolled in the next higher dose group; if one of the three patients in a certain dose group has DLT, three patients in the group will be supplemented with the same dose and method. If DLT occurred in 1 or more of the 3 cases, the dose increase was stopped. The former dose was defined as MTD; if DLT did not occur in 3 cases, the dose increased to the next group. Dose escalation is not allowed for the same patient.

Biological: TAEST16001 cells

Interventions

TAEST16001 cells BIOLOGICAL

The patients in the dose increasing part and the expanding part received the intravenous reinfusion of TAEST16001 cells on the 5th day (i.e. the interval was 4 days) after the lymphocyte elimination chemotherapy: If the dose level of reinfusion was 1 and 2, the planned total amount of TAEST16001cells (calculated by TCR-T positive cells) was given a single reinfusion on the 1st day of the study. If the dose level of reinfusion was 3 and 4,then the total amount of TAEST16001cells (calculated by TCR-T positive cells) was planned to be reinjected in 60% and 40% proportion on the first and second day of the study. After the first reinfusion of TAEST16001 cells, the patients will be given a small dose of IL-2 subcutaneously (study day 1 to day 14), 500000 U / time. The first injection will be carried out within 30 minutes after the cell reinfusion, twice a day (interval 10-12 hours), for 14 days.

TAEST16001 cells treat tumor antigen NY-ESO-1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The informed consent form (ICF) (genotype and tumor antigen screening and primary screening) should be signed before any research related operation;
• Age ≥ 18 years and ≤ 70 years;
• Advanced solid tumor with definite pathological diagnosis;
• Unresectable advanced solid tumor that fails to undergo standard treatment (disease progression or recurrence or intolerable, such as chemotherapy, radiotherapy, targeted treatment, etc.) or lacks effective treatment:
• \) Soft tissue sarcoma: a) Soft tissue sarcoma failed to be treated by chemotherapy containing doxorubicin and ifosfamide; 2) Primary liver cancer: a) Child Pugh liver function score A within 7 days before cell reinfusion; 3) Ovarian cancer: a) Platinum based chemotherapy (such as paclitaxel combined with carboplatin) failed. 4) Non small cell lung cancer (NSCLC): a) failure (disease progression or toxicity intolerance) or lack of effective treatment method of previous standard treatment (including platinum chemotherapy scheme or driven gene targeted treatment); 5) Breast cancer: a) patients who have received standard treatment failure or not applicable standard treatment.
• 、At least 1 measurable lesion (according to recist1.1 standard） 6、Genotype and tumor antigen screening must meet the following two criteria: 1) HLA-A \* 02:01 positive; 2) NY-ESO-1 positive: immunohistochemistry positive cells ≥ 20%; 7、ECOG score 0-1 and expected survival time \> 3 months; 8. Color Doppler echocardiography indicates left ventricular ejection fraction ≥ 50%; 9. Laboratory test results should at least meet the following criteria:
• White blood cell count ≥ 3.0 × 109 / L
• Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L (without the support of G-CSF and GM-CSF, at least 14 days before CLT);
• Absolute lymphocyte count (ALC) ≥ 0.7 × 109 / L;
• Platelet (PLT) ≥ 75 × 109 / L (no transfusion treatment 14 days before CLT);
• Hemoglobin ≥ 10g / dl (no transfusion treatment 14 days before CLT);
• Prothrombin time international INR ≤ 1.5 × ULN, unless anticoagulant therapy is used;
• APTT ≤ 1.5 × ULN, unless anticoagulant therapy is used;
• Serum creatinine ≤ 1.5mg/dl (or 132.6 μ mol / L)
• Creatinine clearance ≥ 60ml / min;

You may not qualify if:

• The last dose of anti-tumor therapy (chemotherapy, endocrine therapy, targeted therapy, immunotherapy, tumor embolization or traditional Chinese medicine / Chinese herbal medicine with anti-tumor indications) was received within 4 weeks before cell reinfusion;
• The live attenuated vaccine had been inoculated within 4 weeks before cell reinfusion;
• The patients with bone metastasis in the whole body;
• It is known that any component used in the treatment of this study will produce allergy Response;
• Not recovered from previous operation or treatment-related adverse reactions to \< 2-level CTCAEv5.0;
• Patients with a history of meningeal or central nervous system metastasis, or patients with clear basic diseases of central nervous system and left significant symptoms within 6 months before cell transfusion;
• Patients with poor drug control hypertension (systolic blood pressure \> 160mmhg and / or diastolic blood pressure \> 90mmHg) or with clinical significance Cardiovascular and cerebrovascular diseases, such as cerebrovascular accident (within 6 months prior to signing the master informed consent), myocardial infarction (within 6 months prior to signing the master informed consent), unstable angina pectoris, congestive heart failure with NYHA grade II or above, or serious arrhythmia that cannot be controlled by drugs or has potential impact on research and treatment Results of ECG showed clinically significant abnormality or average QTCF ≥ 450ms;
• Combined with other serious organic or mental diseases;
• Suffering from systemic active infection requiring treatment, including but not limited to active tuberculosis, known HIV positive patients or clinical active hepatitis A, B and C Patients with inflammation, including virus carriers, should be excluded;
• Patients with autoimmune diseases: those with inflammatory bowel disease history and those with autoimmune disease history determined by the researchers as unsuitable for this study, such as systemic lupus erythematosus, vasculitis, and invasive lung disease, should be excluded (except vitiligo subjects);
• Those with cell transfusion within 4 weeks before and during the study should be used (if there is a long-term plan) Use) systemic sterols, hydroxyurea, immunomodulators (e.g., interferon α or γ, GM-CSF, mTOR inhibitors, cyclosporin, thymosin, etc.);
• History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy;
• Diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease, or liver failure that are not known to be controlled;
• Alcohol and / or drug abusers;
• Pregnant or lactating women;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Guangdong Xiangxue Precision Medical Technology Co., Ltd.: collaborator

Study Sites (1)

Xing Zhang

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Pan Q, Weng D, Liu J, Han Z, Ou Y, Xu B, Peng R, Que Y, Wen X, Yang J, Zhong S, Zeng L, Chen A, Gong H, Lin Y, Chen J, Ma K, Lau JYN, Li Y, Fan Z, Zhang X. Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A *02:01 patients with advanced soft tissue sarcoma. Cell Rep Med. 2023 Aug 15;4(8):101133. doi: 10.1016/j.xcrm.2023.101133.

  PMID: 37586317 DERIVED

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Xing Zhang, professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice director of department of medical sarcoma and melanoma,Principal Investigator,Clinical Professor

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 24, 2020
• Study Start: March 19, 2020
• Primary Completion: April 15, 2022
• Study Completion: May 1, 2024
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (1)