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

An Open-label, Multicenter, Phase II Single Arm Trial of SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV
• Intervention / Treatment: Drug: GM-CSF; Drug: Sintilimab; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Anticipated): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: SBRT + sintilimab + GM-CSF

Drug: GM-CSF; Patients will receive GM-CSF 125μg/m2 daily for 14 consecutive days after completing SBRT treatment.; Drug: Sintilimab; Patients will receive Sintilimab 200 mg every 3 weeks up to 2 years after completing SBRT treatment.; Radiation: SBRT; Patients will receive SBRT for one previously unirradiated primary or metastatic lesion (size: 1-5cm). 24 Gy in 3 fractions (8Gy/Fx) administered once-daily for 3 consecutive days.; Other Names: Stereotactic body radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Objective Response Rate	ORR was defined as the proportion of participants with partial response (PR) or complete response (CR) to treatment as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.	At least 6 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.	Two years
Overall Survival	OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.	Two years
Objective Response Rate (ORR) in Non-irradiated Lesion	Objective Response Rate (ORR) in Non-irradiated Lesion was defined as the proportion of patients with at least 30% reduction from baseline in the longest diameter of any of non-irradiated target lesions defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time-point from the date of treatment initiation to the date of last follow-up.	At least 6 weeks after start of treatment
Progression Free Survival	PFS was measured from the date of enrollment to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death due to any cause, whichever occurred first.	Two years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Study Director: Xinghao Ai, Shanghai Chest Hospital; Study Director: Zhengbo Han, Shengjing Hospital; Study Director: Qian Chu, Tongji Hospital; Study Director: Xiaorong Dong, Union Hospital; Study Director: Lin Wu, Hunan Cancer Hospital

Publications and helpful links

General Publications

• Ni J, Zhou Y, Wu L, Ai X, Dong X, Chu Q, Han C, Wang X, Zhu Z. Sintilimab, stereotactic body radiotherapy and granulocyte-macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial. Radiat Oncol. 2021 Sep 15;16(1):177. doi: 10.1186/s13014-021-01905-3.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 30, 2019
• Primary Completion (ANTICIPATED): August 31, 2022
• Study Completion (ANTICIPATED): August 31, 2023

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (ACTUAL): September 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: Sword

Drug and device information, study documents

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