A Single-Arm Clinical Study of Autologous Tumor-Infiltrating Lymphocyte Infusion (GT201) in Combination With PD-1 Inhibitor for Advanced Head and Neck Tumors
Overview
- Phase
- Not Applicable
- Intervention
- GT201 in combination with PD-1 inhibitors
- Conditions
- HNSCC
- Sponsor
- Grit Biotechnology
- Enrollment
- 32
- Locations
- 2
- Primary Endpoint
- Incidience and severity of adverse events per CTCAE 5.0
- Status
- Recruiting
- Last Updated
- 8 days ago
Overview
Brief Summary
This study is a single-arm early exploratory clinical study. designed to evaluate the safety and tolerability of GT201 in combination with a PD-1 inhibitor for the treatment of advanced head and neck tumor subjects with safety and tolerability, as well as pharmacokinetic characterization and efficacy The study consists of two phases.
The study consists of two phases, a dose-escalation phase and a dose-expansion phase.
Detailed Description
Primary objectives a. To assess the safety and tolerability of GT201 in combination with PD-1 inhibitor in the treatment of advanced head and neck tumors. Secondary Objectives 1. To assess the efficacy of GT201 in combination with PD-1 inhibitors in the treatment of advanced head and neck tumors according to RECIST v1.1. 2. To monitor the pharmacokinetics of GT201 infusion in the treatment of advanced head and neck tumors: duration of back infusion of GT201 in subjects, evaluate expansion status, and correlation with the effectiveness of GT201 infusion. To characterize serum levels of T cell related cytokines such as TNF-α, IFN-γ, IL-6. Purpose of exploratory study To analysis the changes of cell phenotypes and distribution of cell populations. To track the expansion of TIL clones by detecting T cell receptors (TCR)and other possible cytokines in peripheral blood.
Investigators
Eligibility Criteria
Inclusion Criteria
- •1\. Voluntarily join the study, signed informed consent form,, willing and able to comply with the study protocol;
- •2\. Age 18 to 70 years old;
- •3\. Diagnosis with recurrent or metastatic head and neck malignant tumors and received≤2 lines of systemic therapy;
- •4\. Have at least one measurable lesion that is untreated with radiotherapy or other local therapies, is accessible for tumor tissue collection (assessed by the investigator), and can provide a tissue block with a mass ≥1.0 g (approximately 1.5 cm in diameter) for autologous tumor-infiltrating lymphocyte (TIL) preparation. The tissue collection procedure should be minimally invasive whenever possible.
- •5\. After tumor sampling, have at least one measurable lesion as defined by RECIST v1.
- •6\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- •7\. Expected survival time of ≥ 12 weeks;
- •8\. Adequate function of major organs, with the following requirements (administration of any blood components or cell growth factors is not allowed within 14 days prior to surgery):
- •Hematology:
- •Absolute Neutrophil Count (ANC) ≥ 1.0×10⁹/L;
Exclusion Criteria
- •1\. Uncontrolled local or systemic infections of the oral cavity, head, or neck; any active autoimmune disease, history of autoimmune disease, or disease requiring systemic corticosteroid therapy or immunosuppressive drugs (prednisone equivalent dose \> 10 mg/day).
- •2\. Subjects with uncontrollable tumor-related pain assessed by the investigator. Subjects requiring analgesic treatment must be on a stable analgesic regimen at study entry; symptomatic lesions eligible for palliative radiotherapy should have completed treatment prior to study entry.
- •3\. Bleeding events occurring within 3 months prior to screening, including but not limited to gastrointestinal bleeding caused by fundic or esophageal varices, increased bleeding risk due to portal hypertension, active gastrointestinal bleeding, etc.; or subjects assessed by the investigator as having a high risk of major bleeding, including but not limited to tumors encasing or invading major blood vessels \[i.e., carotid artery, jugular vein, bronchial artery\] and/or exhibiting other high-risk features (e.g., fistula, significant cavitary lesions, history of bleeding \[≤ 60 days from signing the ICF\]).
- •4\. Arterial/venous thrombotic events occurring within 6 months prior to screening, such as cerebrovascular accident, deep vein thrombosis, and pulmonary embolism.
- •5\. A history of interstitial pneumonia, clinically significant active pneumonia at screening, or other respiratory diseases that severely impair pulmonary function.
- •6\. A history of clinically significant cardiovascular disease, including but not limited to: (1) congestive heart failure (NYHA class \> 2); (2) unstable angina pectoris; (3) myocardial infarction within the past 3 months; (4) any supraventricular or ventricular arrhythmia requiring treatment or intervention.
- •7\. Subjects with ≥ 3 untreated central nervous system (CNS) metastases at screening. Exclusion exception: Subjects with ≤ 3 CNS metastases, with the largest lesion \< 1 cm in diameter, no peritumoral edema on brain imaging (MRI or CT), and no evidence of progressive CNS disease on brain imaging for at least 3 months after treatment may be enrolled.
- •8\. Ineligible for enrollment if spinal cord compression has not been relieved by surgery and/or radiotherapy. Exclusion exception: Subjects with active CNS metastases are excluded, except for those with stable brain metastases who have not required medical treatment for 3 months and are not dependent on corticosteroids.
- •9\. A history of malignant tumors other than the target indication within 5 years prior to screening (excluding adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, and breast ductal carcinoma in situ after radical resection), unless the investigator determines that the benefits to the subject outweigh the risks.
- •10\. Presence of refractory or intractable epilepsy, massive pleural effusion, ascites, pericardial effusion, etc., that cannot be controlled by medication, or contraindications to interleukin-2 (IL-2) use.
Arms & Interventions
GT201 in combination with PD-1 inhibitors treatment group
Intervention: GT201 in combination with PD-1 inhibitors
Outcomes
Primary Outcomes
Incidience and severity of adverse events per CTCAE 5.0
Time Frame: 3 years
To characterize the safety profile of autologous TIL injection (GT201) in patients with relapsed/metastatic advanced solid tumor as measured by the incidience and severity of adverse events per CTCAE 5.0