Gut Microbial Metabolites Inosine Combined With PD-1/PD-L1 Inhibitor for Patients With Malignant Advanced Solid Tumors

NCT05809336 | Completed Phase 2

• 1 other identifier: Beijing inosine
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

We conducted a single-center, prospective randomized ,Parallel controls, open labels Clinical Studies,The study is about Gut Microbial Metabolites Inosine Combined With PD-1/PD-L1 Inhibitor for Patients with malignant Advanced Solid Tumors .One group was the inosine group , the other group was the non-inosine group.The treatment regimen of inosine group : inosine + PD-1/PD-L1 inhibitor ± chemotherapy/targeting, and the treatment regimen of non-inosine group : PD-1/PD-L1 inhibitor ± chemotherapy/targeting.The primary study endpoints were overall survival (OS) and progression-free survival PFS, and the secondary study endpoints were objective remission rate (ORR) and disease control rate (DCR) comparing the two groups.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• overall survival (OS)

  Time from randomization grouping to death from any cause

  36 months

• progression-free survival (PFS)

  Time from randomization grouping to the first recorded disease progression or death from any cause

  36 months

Secondary Outcomes (2)

• objective remission rate(ORR) [ Time Frame: Up to 36 months ]

  36 months

• disease control rate (DCR)

  36 months

Study Arms (2)

inosine group

EXPERIMENTAL

Participants will receive inosine + PD-1/PD-L1 inhibitor ± chemotherapy/targeting,every 2 or 3 weeks, until the subject's disease progresses, death, intolerable adverse events, the investigator determines that there is no benefit from continued treatment or other termination criteria are met (pregnancy, individual patient reasons or co-morbidities), the subject requests withdrawal from the study, withdrawal of informed consent, and loss of visit

Drug: Inosine 0.2g orally 3 times/day

non-inosine group

ACTIVE COMPARATOR

Participants will receive PD-1/PD-L1 inhibitor ± chemotherapy/targeting, every 2 or 3 weeks .until the subject's disease progresses, death, intolerable adverse events, the investigator determines that there is no benefit from continued treatment or other termination criteria are met (pregnancy, individual patient reasons or co-morbidities), the subject requests withdrawal from the study, withdrawal of informed consent, and loss of visit

Drug: PD-1/PD-L1 inhibitor ,chemotherapy/targeting

Interventions

Inosine 0.2g orally 3 times/day DRUG

inosine + PD-1/PD-L1 inhibitor ± chemotherapy/targeting,

Also known as: Camrelizumab for injection, Sintilimab injection, Penpulimab injection, Tislelizumab injection, Pembrolizumab injection, Toripalimab, Atezolizumab, chemotherapy/targeting

inosine group

PD-1/PD-L1 inhibitor ,chemotherapy/targeting DRUG

PD-1/PD-L1 inhibitor ± chemotherapy/targeting

Also known as: Camrelizumab for injection, Sintilimab injection, Penpulimab injection, Tislelizumab injection, Pembrolizumab injection, Toripalimab, Atezolizumab, chemotherapy/targeting

non-inosine group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed unresectable locally advanced, recurrent or metastatic solid tumors
• Age 18 years old - 75 years old
• ECOG score of ≤ 2
• Time to end of palliative treatment for localized lesions (non-target lesions) was \>3 weeks from randomization start time, At least one measurable lesion or assessable lesion according to RECIST v1.1
• Can provide archived pathological tissues or fresh pathological tissues for PD-L1, MMR/MSI, TMB testing within 6 months from the signing of the informed consent for screening and can obtain the test results
• Adequate organ and bone marrow function, defined as follows: 1) Blood count: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count (PLT) ≥ 100 × 109/L, hemoglobin level (HGB) ≥ 9.0 g/dL. 2) Liver function: patients without liver metastases require: serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal ( ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. patients with liver metastases required: TBIL ≤1.5×ULN; ALT and AST ≤5×ULN. 3) renal function: creatinine clearance (Ccr) ≥50mL/min (calculated using the Cockcroft/Gault formula): female: Ccr = (140-years-old) × body weight (kg) × 0.85; men: Ccr = (140-years-old) × body weight (kg) × 1.00. 4) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN
• Expected survival time ≥ 12 weeks
• Female subjects of childbearing age or male subjects whose sexual partners are women of childbearing age are required to use effective contraception throughout the treatment period and for 6 months after the treatment period
• Sign the written informed consent

You may not qualify if:

• Signs of active bleeding or perforation
• History of intestinal obstruction or the following diseases: inflammatory bowel disease or extensive bowel resection, Crohn's disease, ulcerative colitis
• Hepatic metastatic focal load of approximately 50% or more of the entire liver volume
• Antibiotic was used within 2 weeks before study treatment
• Received systemic antitumor therapy with herbs or immunomodulatory drugs (including thymidine, interferon, interleukin, etc.) within 2 weeks before the first dose.
• immunosuppressive drugs was used within 4 weeks before study treatment, excluding topical glucocorticoids or physiologic doses of systemic glucocorticoids (i.e., no more than 10mg/day of prednisone or equivalent doses of other glucocorticoids) of nasal spray, inhalation, or other routes, or glucocorticoid for the prevention of contrast allergy
• Interstitial lung disease requiring glucocorticoid therapy
• Active, known or suspected autoimmune disease or history of the disease within the last 2 years (patients with vitiligo, psoriasis, alopecia or Grave's disease not requiring systemic treatment within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy, and type I diabetes requiring only insulin replacement therapy may be enrolled)
• Symptomatic congestive heart failure (New York Heart Association class -≥3) or symptomatic or poorly controlled arrhythmias
• standard treatment could not uncontrollarterial hypertension (systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 100).
• Any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, within 6 months prior to enrollment in treatment
• History of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolism within 3 months prior to enrollment
• Known active tuberculosis
• Known history of case type immunodeficiency virus infection
• Positive hepatitis B surface antigen and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) titer test ≥ 1×104 copies/mL (or HBV-DNA quantification ≥ 2000 units/ml); active hepatitis C

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Qin li

Beijing, Beijing Municipality, 100029, China

Location

Related Publications (1)

• Zhao H, Zhang W, Lu Y, Dong Y, He Z, Zhen H, Li Q. Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study. Cancer Med. 2024 Sep;13(17):e70143. doi: 10.1002/cam4.70143.

  PMID: 39267574 DERIVED

MeSH Terms

Interventions

Inosine; camrelizumab; Injections; sintilimab; penpulimab; tislelizumab; pembrolizumab; toripalimab; atezolizumab; Drug Therapy

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Therapeutics

Study Design

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

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: April 12, 2023
• Study Start: May 1, 2019
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: April 12, 2023

Record last verified: 2023-03

Locations

CN (1)