PRaG-1 Plus PRaG Therapy in Advanced Solid Tumors: A Prospective Clinical Trial (PRaG 10.0)

The goal of this clinical trial is to learn if a combination treatment using PRaG-1 Cordycepin Tablets with radiation therapy, immune-boosting injections, and immunotherapy drugs can help patients with advanced solid tumors. It will also assess safety. The main questions it aims to answer are:

Does this treatment improve immune function and slow tumor growth? What side effects or risks occur during treatment?

Participants will:

Take PRaG-1 Cordycepin Tablets (a natural compound derived from Cordyceps fungus) orally: higher dose for 7 days before radiation, then lower daily dose for 2 weeks Receive targeted radiation therapy to the tumor area (5-12 Gy total in 2-3 sessions) Get daily immune-boosting injections (GM-CSF) for 7 days starting with radiation Receive immunotherapy drugs (PD-1/PD-L1 inhibitors) within one week after radiation Have blood drawn and small tumor tissue samples taken before and after the first two treatment cycles for immune analysis All participants will receive this combination treatment; there is no placebo or alternative treatment group in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphopenia; Radiotherapy; Solid Cancer; Immune Checkpoint Inhibitor
• Intervention / Treatment: Drug: PD -1/PD-L1 monoclonal antibody

Detailed Description

1. This clinical study utilizes PRaG-1 Cordycepin Tablets (oral administration) to modulate immune cell and cytokine profiles. Lymphocyte subset analysis is performed before and after treatment to quantify immune function changes.

2. Treatment phases:

   Cordycepin: PRaG-1 Cordycepin Tablets (manufactured by Life Origin Biotechnology Co., Ltd., affiliated with the National Bioengineering Engineering Technology Center, Nanjing Tech University) contain 200 mg cordycepin per tablet and hold National Food Production License No. SC11332019200201.

   Loading dose: Initiated 1 week prior to radiotherapy, administered as 2 tablets once daily after meals with water for 7 consecutive days.

   Maintenance dose: Following loading dose completion, 1 tablet once daily after meals with water is continued starting with radiotherapy for 2 weeks per cycle (every 3 weeks). Efficacy is assessed at each cycle.

   Biospecimen collection: 5 mL blood and 2 g tumor biopsy tissue are obtained before and after the first two treatment cycles for immune function analysis (including bulk RNA sequencing, single-cell sequencing, TCR sequencing, proteomic analysis, metabolomic analysis, gut microbiome analysis, and urinary extracellular vesicle analysis).

   Treatment discontinuation criteria: Confirmed disease progression, intolerable toxicity, withdrawal of informed consent, death, or other protocol-specified criteria.

   Radiotherapy: Begins on Day 1 of the treatment cycle; 5-12 Gy total dose delivered in 2-3 fractions per lesion, once daily.

   GM-CSF: 200 μg subcutaneously daily starting on radiotherapy day, continued for 7 days.

   Immunotherapy: PD-1/PD-L1 inhibitors initiated within one week post-radiotherapy.

3. Maintenance phases:

Stage A: ≥2 cycles of cordycepin combined with radiotherapy, PD-1/PD-L1 inhibitors, and GM-CSF.

Stage B: Maintenance therapy with PD-1/PD-L1 inhibitors, GM-CSF, and cordycepin for ≥6 months.

Stage C: Continued PD-1/PD-L1 inhibitor monotherapy until disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liyuan Zhang, Doctor; Phone Number: 051267784829; Email: zhangliyuan126@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histologically confirmed treatment-naïve or relapsed/metastatic advanced solid malignancies with no standard treatment option per current clinical guidelines or intolerance to standard therapy; measurable metastatic lesions ≥1 cm (by RECIST criteria); absolute lymphocyte count (ALC) below lower limit of normal (LLN).
3. No history of congestive heart failure, unstable angina, or unstable cardiac arrhythmias within the past 6 months.
4. ECOG performance status 0-3; estimated life expectancy ≥3 months.
5. No history of significant hematologic, cardiac, pulmonary, hepatic, or renal dysfunction.
6. Baseline AST ≤3×ULN and ALT ≤3×ULN (≤5×ULN for hepatocellular carcinoma or liver metastases); creatinine ≤3×ULN.
7. Capacity to comprehend study procedures and voluntarily provide written informed consent.

Exclusion Criteria:

1. History of other malignancies within the past 5 years, except for adequately treated non-melanoma skin cancer or cervical carcinoma in situ.
2. Uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders that, in the investigator's judgment, may interfere with informed consent or treatment adherence.
3. Clinically significant active cardiac disease, including symptomatic coronary artery disease, NYHA Class II or higher congestive heart failure, severe arrhythmias requiring pharmacological intervention, or myocardial infarction within the past 12 months.
4. History of solid organ transplant requiring ongoing immunosuppressive therapy.
5. Known significant active infection, or significant hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction, or other serious uncontrolled comorbidities as determined by the investigator.
6. Allergy to any component of the study drug(s).
7. History of immunodeficiency, including HIV infection, acquired or congenital immunodeficiency disorders, solid organ transplant, or chronic immunosuppressive therapy for immune-related conditions.
8. Active or latent tuberculosis infection confirmed by positive T-SPOT.TB test or chest X-ray findings suggestive of tuberculosis.
9. Any other condition that, in the investigator's clinical judgment, may compromise study participation or safety.

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: treatment	Drug: PD -1/PD-L1 monoclonal antibody; PRaG-1 Cordycepin Tablets+ Radiotherapy+ GM-CSF+ PD-1/PD-L1 inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate #ORR#	Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from the first administration of study treatment to the first occurrence of disease progression as determined by investigator using RECIST v1.1 or death from any cause, whichever comes first.	36 months
Disease control rate (DCR)	DCR was defined as the percentage of participants with a complete response (CR), partial response (PR), or stable disease (SD).	36 months
Adverse event	rate of adverse events	36 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Immune System Diseases; Leukocyte Disorders; Hematologic Diseases; Immunologic Deficiency Syndromes; Leukopenia; Hemic and Lymphatic Diseases; Lymphopenia
• Other Study ID Numbers: JD-LK2025017-IR01

Drug and device information, study documents

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