SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC

Fudan University

Status and phase

Unknown

Phase 2

Conditions

NSCLC Stage IV

Treatments

Drug: GM-CSF

Drug: Sintilimab

Radiation: SBRT

Study type

Interventional

Funder types

Other

Identifiers

NCT04106180

Sword

Details and patient eligibility

About

This study is an open-label, multicenter, phase II single arm trial to evaluate the efficacy and safety of SBRT in combination with sintilimab and GM-CSF for the treatment of patients with advanced NSCLC.

Enrollment

63 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age at least 18 years.
ECOG PS 0-1.
Pathologically confirmed stage IV NSCLC.
Negative for driver genes including EGFR，ALK，and ROS-1.
Patients with disease progression after first-line platinum-based therapy without anti-PD-1 or PD-L1 treatment.
Patients with at least one lesion (size 1-5cm) eligible for SBRT (24Gy/3Fx) and simultaneously at least one measurable lesion (in addition to the lesion treated with SBRT) as defined by RECIST1.1.
Patients with brain metastasis are eligible if they are asymptomatic, neurologically stable, and off corticosteroids.
Life expectancy of more than 3 months.
Patients with no indications for palliative radiotherapy in the opinion of the investigator.
Patients with a prior history of surgery are eligible if they have recovered adequately from the toxicity and/or complications of surgery.
Signed informed consent for the use of fresh tumor biopsies before and during the treatment.
Women of childbearing age and men must agree to use effective contraception during the trial.
Adequate organ function within 1 week prior to the enrollment：
1. Adequate bone marrow function: hemoglobin ≥80g/L, white blood cell (WBC) count ≥ 4.0 * 10 ^ 9/L or neutrophil count ≥ 1.5 * 10 ^ 9/L, and platelet count ≥ 100 * 10 ^ 9/L;
2. Adequate hepatic function: total bilirubin < 1.5 x upper limit of normal (ULN). Note: If total bilirubin is > 1.5 x ULN, direct bilirubin must ≤ ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN;
3. Adequate renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min;
Ability to understand and willingness to provide the informed consent.

Exclusion criteria

Prior exposure to immunomodulatory agent,including but limited to anti-PD-1 or anti-PD-L1 antibodies.
Severe autoimmune disease: inflammatory bowel disease (including Crohn's disease and ulcerative colitis) 、rheumatoid arthritis、scleroderma、systemic lupus erythematosus 、Wegener's granulomatosis and related vasculitides.
Patients receiving non-platinum-based chemotherapy as first-line treatment
Mixed small cell with non-small cell lung cancer histology.
Pregnant or lactating women.
Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
History of any other malignancy.
Patients in whom palliative radiotherapy is indicated in the opinion of the investigator.
Active infection, congestive heart failure, myocardial infarction within the 6 months prior to enrollment, unstable angina pectoris or cardiac arrhythmia.
Prior allergic reaction or contraindications to sintilimab and GM-CSF.
Patients who have received tumor vaccine; or administration of live, attenuated vaccine within 4 weeks before the start of treatment. Note: Influenza vaccination is permitted only during influenza season, while live, attenuated influenza vaccine such as FluMist is not allowed.
Patients receiving concurrent chemotherapy drugs,other immunosuppressive agents,or other investigational treatment.Long-term corticosteroid users are also excluded.
Mental disorders, drug abuse, and social condition that may negatively impact compliance in the opinion of the investigator.