Thymalfasin-based PRaG Mode for Advanced Refractory Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Refractory Tumor
• Intervention / Treatment: Drug: Thymalfasin; Radiation: Radiotherapy; Drug: PD-1/PD-L1 inhibitor; Drug: GM-CSF

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liyuan Zhang; Phone Number: 0512-67784829; Email: zhangliyuan126@126.com

Study Locations

• China
  • Suzhou, China, 215004
    • Recruiting
    • The Second Affiliated Hospital of SchoowUniversity
    • Contact: Liyuan Zhang; Phone Number: +8613375183257; Email: kkyuehong@163.com
    • Principal Investigator: Liyuan Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects aged≥ 18 years;
2. 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);
3. Subjects who have not suffered from congestive heart failure, unstable angina, or unstable arrhythmia in the past 6 months;
4. Subjects who have the ECOG (Eastern Cooperative Oncology Group) performance status score of 0-3 and the life expectancy≥3 months;
5. Subjects who have no serious abnormalities of hematopoietic functions, heart, lung, liver, kidney functions, or immune deficiency in the past;
6. 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.
7. Subjects who shall have the ability to understand and voluntarily sign the informed consent forms.

Exclusion Criteria:

1. Pregnant or lactating women.
2. 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).
3. Subjects who have a history of uncontrolled epilepsy, CNS disease or mental disorder.
4. 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.
5. Subjects who require immunosuppressive therapy for organ transplantation.
6. 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.
7. Subjects who are allergic to any ingredient of the investigational drug.
8. 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.
9. 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).
10. Other conditions that are not suitable for enrollment in the Investigator's opinions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention group; 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; loading dose with thymalfasin based on the amounts of T lymphocyte; Other Names: Thymosin alpha-1; Radiation: Radiotherapy; hypofractionated radiotherapy/SBRT; Drug: PD-1/PD-L1 inhibitor; The PD-1/PD-L1 inhibitors are used within one week after radiotherapy; Other Names: PD-1/PD-L1 antibody; Drug: GM-CSF; subcutaneous injection daily for 7 consecutive days; Other Names: :Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor for Injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University
• Collaborators: SciClone Pharmaceuticals

Publications and helpful links

General Publications

• Kong Y, Zhao X, Xu M, Pan J, Ma Y, Zou L, Peng Q, Zhang J, Su C, Xu Z, Zhou W, Peng Y, Yang J, Zhou C, Li Y, Guo Q, Chen G, Wu H, Xing P, Zhang L. PD-1 Inhibitor Combined With Radiotherapy and GM-CSF (PRaG) in Patients With Metastatic Solid Tumors: An Open-Label Phase II Study. Front Immunol. 2022 Jul 8;13:952066. doi: 10.3389/fimmu.2022.952066. eCollection 2022.
• Giacomini E, Severa M, Cruciani M, Etna MP, Rizzo F, Pardini M, Scagnolari C, Garaci E, Coccia EM. Dual effect of Thymosin alpha 1 on human monocyte-derived dendritic cell in vitro stimulated with viral and bacterial toll-like receptor agonists. Expert Opin Biol Ther. 2015;15 Suppl 1:S59-70. doi: 10.1517/14712598.2015.1019460. Epub 2015 Jun 22.
• Schulof RS, Lloyd MJ, Cleary PA, Palaszynski SR, Mai DA, Cox JW Jr, Alabaster O, Goldstein AL. A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-alpha 1 in patients with lung cancer. J Biol Response Mod. 1985 Apr;4(2):147-58.
• Liu F, Qiu B, Xi Y, Luo Y, Luo Q, Wu Y, Chen N, Zhou R, Guo J, Wu Q, Xiong M, Liu H. Efficacy of Thymosin alpha1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043). Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):433-443. doi: 10.1016/j.ijrobp.2022.07.009. Epub 2022 Jul 21.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2023
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 29, 2023
• First Posted (Actual): March 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Immune Checkpoint Inhibitors; Thymalfasin
• Other Study ID Numbers: JD-LK-2022-151-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No