SBRT for Oligo-residual NSCLC After Treatment With PD-1/PD-L1 Immune Checkpoint Inhibitors

An Open-label, Multicenter, Phase II Single Arm Trial of Stereotactic Body Radiotherapy for Oligo-residual Disease After Effective Treatment With PD-1/PD-L1 Inhibitors Among Metastatic Non-small Cell Lung Cancer

Despite the impressive response rate to PD-1/PD-L1 immune checkpoint inhibitors, resistance inevitably develops in most patients. Stereotactic body radiation therapy (SBRT) plays a growing role in the management of oligometastatic disease. This study aims to evaluate the efficacy and safety of SBRT for oligo-residual NSCLC after effective treatment with PD-1/PD-L1 inhibitors.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV
• Intervention / Treatment: Drug: PD-1/PD-L1 inhibitors (alone or in combination with chemotherapy); Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhengfei Zhu, MD; Phone Number: +86-18017312901; Email: fuscczzf@163.com
• Study Contact Backup: Name: Jianjiao Ni, MD; Phone Number: 13761974092; Email: nijianjiao8@sina.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhengfei Zhu, MD; Phone Number: +86-18017312901; Email: fuscczzf@163.com
    • Contact: Jianjiao Ni, MD; Phone Number: 13761974092; Email: nijianjiao8@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age at least 18 years.
• ECOG PS 0-1.
• Patients with pathologically confirmed stage IV NSCLC by tumor biopsy and/or fine-needle aspiration.
• Negative for driver genes including EGFR, ALK, and ROS-1.
• Oligo-residual disease after effective treatment with PD-1/PD-L1 inhibitors that would be amenable to SBRT in the opinion of the investigator.
• Patients with brain metastasis are eligible if they are asymptomatic, neurologically stable, and off corticosteroids.

• Patients with a history of radiotherapy are eligible if they satisfy the following criteria:

  1. Radiotherapy administered more than 4 weeks before study entry.
  2. At least one measurable lesion outside the radiation field.
• 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 sufficiently recovered 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.
• Life expectancy of more than 3 months.

• Adequate organ function within 1 week prior to 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:

• 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.
• Symptomatic interstitial lung disease or clinically active infectious/non-infectious pneumonitis.
• History of another malignancy or concurrent malignancy.
• Active infection, congestive heart failure, or any evidence of myocardial infarction, unstable angina pectoris or cardiac arrhythmia within 6 months prior to enrollment.
• Any evidence of severe or uncontrolled systemic diseases, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
• Patients in whom palliative radiotherapy is indicated in the opinion of the investigator.
• Mixed small cell with non-small cell lung cancer histology.
• The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.
• 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 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 investigator's opinion.
• Prior allergic reaction or contraindications to PD-1/PD-L1 inhibitors.

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: SBRT for oligo-residual NSCLC

Drug: PD-1/PD-L1 inhibitors (alone or in combination with chemotherapy); Patients will receive PD-1/PD-L1 inhibitors for up to 2 years or until confirmed progression or unacceptable toxicity. PD-1/PD-L1 inhibitors will be administrated as an intravenous(IV) infusion.; Radiation: SBRT; Patients with oligo-residual NSCLC after effective treatment with PD-1/PD-L1 inhibitors will be treated with curative-intent SBRT of residual lesions. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist. PD-1/PD-L1 inhibitors will be withheld one day before the treatment and resumed within 2 weeks after completion of SBRT.; Other Names: Stereotactic body radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS was measured from the date of the initiation of treatment with PD-1/PD-L1 inhibitors to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death.	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.	Two year

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhengfei Zhu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): June 30, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2024

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; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2020-NSCLCSBRT-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No