PRaG Regimens Rechallenge for Patients With Resistance to PD1/PD-L1 Inhibitors in Refractory Advanced Solid Tumors.

NCT05530200 | Unknown Phase 2

• 1 other identifier: JD-LK-2022-102-01
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

Finding an effective treatment to rescue with resistance of PD-1/PD-L1 inhibitor has been an urgent problem.The PRaG trial as a salvage therapy in advanced solid tumors has obtained satisfactory results.We found that patients with PD-1/PD-L1 inhibitors resistance are more likely to benefit from the PRaG regimens(PD-1 inhibitors combined with radiotherapy and GM-CSF with IL-2). Further phase II clinical trial was conducted to confirm the efficacy and safety of PRaG regimen rechallenge for patients with resistance to PD1/PD-L1 inhibitors in refractory advanced solid tumors.

Conditions

Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (1)

• ORR

  objective response rate

  Up to 3 years

Secondary Outcomes (4)

• PFS

  Up to 3 years

• DCR

  Up to 3 years

• OS

  Up to 3 years

• Treatment Related Severe Adverse Effects

  Up to 3 years

Study Arms (1)

Radiotherapy, PD-L1 inhibitors Sequential GM-CSF and IL-2

EXPERIMENTAL

Radiation: Hypofractionated radiotherapy; Drug: PD-L1 inhibitor; Drug: GM-CSF; Drug: IL-2

Interventions

Hypofractionated radiotherapy RADIATION

24Gy/8Gy/3f

Radiotherapy, PD-L1 inhibitors Sequential GM-CSF and IL-2

PD-L1 inhibitor DRUG

q3w

Radiotherapy, PD-L1 inhibitors Sequential GM-CSF and IL-2

GM-CSF DRUG

200μg, D1-D7

Radiotherapy, PD-L1 inhibitors Sequential GM-CSF and IL-2

IL-2 DRUG

at a dose of 2 million IU, D8-D14

Radiotherapy, PD-L1 inhibitors Sequential GM-CSF and IL-2

Eligibility Criteria

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

You may qualify if:

• Aged≥18 years;
• The patients must conform to the advanced solid cancer with multiple metastases(may be accompanied by metastasis of other organs),progression after first-line systemic therapy and have clear pathological diagnosis report;
• Disease progression after PD-1/PD-L1 therapy in the past, except for the permanent discontinuation of the drug due to immune-related toxicity of grade 3 or above;
• Enrolled patients must improve the detection of PD-L1, TMB, MSI and other immune-related indicators;
• No congestive heart failure, unstable angina pectoris, unstable arrhythmia within the past 6 months;
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-3, and life expectancy 3 months or more;
• There was no history of serious hematopoietic function, abnormal heart, lung, liver, kidney function and immune deficiency;
• One week before enrollment,absolute value of T lymphocytes≥0.5 times of normal lower limit,neutrophil ≥ 1.0×109/L,AST and ALT ≤3.0 times normal upper limit(Liver cancer/liver metastasis patients ≤5.0 times normal upper limit),creatinine ≤ 3.0 times normal upper limit,serum calcium≥2.0mmol/L;
• Patients must have the ability to understand and voluntarily sign an informed consent form.

You may not qualify if:

• Pregnant or lactating women;
• Patients with a history of other malignant diseases in the last 2 years,except cured skin cancer and carcinoma in situ;
• Patients with a history of uncontrolled epilepsy, central nervous system diseases or mental disorders, whose clinical severity may hinder the signing of informed consent or affect the patient's compliance with drug treatment as judged by the investigator;
• Clinically significant (ie, active) heart disease, such as symptomatic coronary heart disease, congestive heart failure New York Heart Association (NYHA) Class II or greater, or severe arrhythmia requiring drug intervention, or a history of myocardial infarction within the last 12 months;
• Organ transplantation requiring immunosuppressive therapy;
• Known active infection, or significant hematological, renal, metabolic,gastrointestinal, endocrine function or metabolic disorders, or other serious uncontrolled concomitant diseases as judged by the investigator;
• Hypersensitivity to any component of the study drug;
• History of immunodeficiency, including positive HIV test or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation, or other related diseases requiring long-term oral hormone therapy (greater than 10 mg/d prednisone);
• Patients who are in the period of acute and chronic tuberculosis infection(patients with positive T-spot test and suspicious tuberculosis lesions on chest radiography), are in the period of acute hepatitis infection or have chronic hepatitis B virus copy number higher than the normal range;
• Other conditions considered unsuitable by the investigator.

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Radiation Dose Hypofractionation; Immune Checkpoint Inhibitors; Granulocyte-Macrophage Colony-Stimulating Factor; Interleukin-2

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Lymphokines

Central Study Contacts

Meiling Xu

CONTACT

+8615106203097; xumeiling1115@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2022
• First Posted: September 7, 2022
• Study Start: September 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share