Thymalfasin-based PRaG Mode for Advanced Refractory Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, single-arm, Phase II investigator-initiated trial of precise thymalfasin-regulated therapy combined with hypofractionated radiotherapy, PD-1/PD-L1 inhibitor sequential GM-CSF for treatment of advanced refractory solid tumors.

Detailed Description
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One cycle of activation cycle includes： Loading dose with thymalfasin was administrated based on the absolute number of T lymphocytes. Radiotherapy (5 or 8Gy three fractions)was administrated to a metastatic lesion. GM-CSF 200ug was subcutaneous injected for seven days from the first day of radiotherapy PD-1/L1 inhibitor was intravenous injected within one week after radiotherapy. At least two activation cycles were administrated. Then maintenance treatment includes： Loading dose with thymalfasin was administrated based on the absolute number of T lymphocytes. GM-CSF 200ug was subcutaneous injected for seven days. PD-1/L1 inhibitor was intravenous injected.

Official Title
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Treatment of Advanced Refractory Solid Tumors Based on Precise Thymalfasin-regulated PRaG Mode: an Open-label, Prospective, Multicenter Study (PRaG 5.0 Study)

Conditions
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Advanced Solid Tumor, Refractory Tumor

Intervention / Treatment
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* Drug: Thymalfasin
* Radiation: Radiotherapy
* Drug: PD-1/PD-L1 inhibitor
* Drug: GM-CSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged≥ 18 years; Enrolled subjects who shall meet the criteria of recurrent or metastatic advanced solid malignant tumors, have a definite pathology diagnosis report or medical history, without definitely recommended standard treatment regimen in the guidelines, and cannot tolerate or are unwilling to receive the standard treatment regimen, and have clear, measurable metastatic lesions (>1cm); Subjects who have not suffered from congestive heart failure, unstable angina, or unstable arrhythmia in the past 6 months; Subjects who have the ECOG (Eastern Cooperative Oncology Group) performance status score of 0-3 and the life expectancy≥3 months; Subjects who have no serious abnormalities of hematopoietic functions, heart, lung, liver, kidney functions, or immune deficiency in the past; Subjects whose AST and ALT levels are ≤3.0 times the upper limit of normal (≤5.0 times the upper limit of normal for patients with liver cancer/metastasis liver carcinoma), and creatinine level is ≤3.0 times the upper limit of normal one week before enrollment. Subjects who shall have the ability to understand and voluntarily sign the informed consent forms. Exclusion Criteria: Pregnant or lactating women. Subjects who have a history of other malignant diseases in the last 5 years, expect for：malignancies that can be cured after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer). Subjects who have a history of uncontrolled epilepsy, CNS disease or mental disorder. Subjects with clinically severe (active) cardiac disease such as symptomatic coronary heart disease, NYHA Class II or worse congestive heart failure, or severe arrhythmias requiring medical intervention, or a history of myocardial infarction within the last 12 months. Subjects who require immunosuppressive therapy for organ transplantation. Subjects with known significant active infection or significant disorders of blood, kidney, metabolism, gastrointestinal, endocrine functions or metabolisms as judged by the Investigator, or other severe, uncontrolled concomitant diseases. Subjects who are allergic to any ingredient of the investigational drug. Subjects who have a medical history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or those with a history of organ transplantation, or those with other immune-related diseases requiring long-term oral hormone therapy. Subjects who are in the stage of acute and chronic tuberculosis infections (positive result of T-spot test, with suspected tuberculous lesions on chest X-ray). Other conditions that are not suitable for enrollment in the Investigator's opinions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>A treatment cycle includes: Loading dose with thymalfasin was administrated based on the absolute number of T lymphocytes. Radiotherapy (5 or 8Gy three fractions)was administrated to a metastatic lesion GM-CSF 200ug was subcutaneous injected for seven days from the first day of radiotherapy PD-1/L1 inhibitor was intravenous injected within one week after radiotherapy | Drug: Thymalfasin<br>* loading dose with thymalfasin based on the amounts of T lymphocyte<br>* Other names: Thymosin alpha-1;Radiation: Radiotherapy<br>* hypofractionated radiotherapy/SBRT<br>Drug: PD-1/PD-L1 inhibitor<br>* The PD-1/PD-L1 inhibitors are used within one week after radiotherapy<br>* Other names: PD-1/PD-L1 antibody;Drug: GM-CSF<br>* subcutaneous injection daily for 7 consecutive days<br>* Other names: :Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor for Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | ORR is defined as the proportion of patients who have a partial (PR) or complete response (CR) to therapy among the total number of evaluable patients. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD) | 24 months | 
| Progression free survival (PFS) | The time from commencement of treatment to disease progression or death from any cause. | 24 months | 
| Overall survival (OS) | The time from the first day of enrollment to death from any cause. | 24 months | 
| Incidence of adverse events | the rate of AE | 24 months |