Immunotherapy With or Without SBRT in Patients With Stage IV Non-small Cell Lung Cancer

A Randomized Trial of Consolidative Immunotherapy With vs Without Thoracic Radiotherapy and / or Stereotactic Body Radiation Therapy (SBRT) After First-Line Systemic Therapy for Metastatic NSCLC

This phase III trial studies immunotherapy and stereotactic body radiation therapy to see how well it works compared with immunotherapy alone after first-line systemic therapy (therapy that goes throughout the body) in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving immunotherapy with stereotactic body radiation therapy may work better than immunotherapy alone in treating patients with non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Lung Cancer; Stage IV Lung Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy; Biological: Pembrolizumab

Detailed Description

PRIMARY OBJECTIVES:

I. To compare progression-free survival of patients randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.

SECONDARY OBJECTIVES:

I. To estimate overall survival in all patients and will compare overall survival of those randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.

II. In patients receiving radiation, to describe the rate of in-field local control and rate of out-of-field disease progression with serial imaging.

III. In patients not receiving radiation, describe progression at known sites of disease after first line systemic therapy and rate of development of new metastases with serial imaging.

IV. To evaluate toxicity associated with radiation followed by consolidative immunotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT). Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.

ARM II: Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, every 6 months for the next 2 years, and then annually for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients who are 18 years or older.
• Performance Status 0-2 (ECOG) at time of consult with radiation oncology.
• Pathologically proven non-small cell lung cancer (NSCLC) with evidence of metastatic disease.
• Must have received 4 cycles of standard of care systemic therapy (usually this will consist of combination chemo-immunotherapy), with a CT chest abdomen pelvis that was performed after completion of these 4 cycles and demonstrates no evidence of progression per RECIST v1.1.
• To be eligible for enrollment and randomization, patients must be within 180 days from their first dose of standard of care systemic therapy. Cycle 1 day 1 is defined as day 1. If enrolled on day 180, the patient would need to be randomized the same day.
• Persistent active disease must be amenable to radiation treatment per the treating radiation oncologist, and patients must have at least one residual site of disease which can be identified by CT or PET/CT and targeted with radiation.
• Patients who previously had earlier stage NSCLC treated definitively and have now developed new distant disease, are eligible for inclusion if they have undergone at least 4 cycles of standard of care systemic therapy for their metastatic recurrence, and they meet all criteria above.
• There are no strict size or tumor number limitations in a given organ (lung, liver, abdomen pelvis, or spine). This is at the discretion of the treating radiation oncologist.

Exclusion Criteria from Enrollment

• More than 180 days has elapsed since day 1 of cycle 1 of standard of care systemic therapy.
• Pregnant or lactating women.
• The patient has received treatment for other carcinomas within the last three years (Except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage 0 or stage I breast cancer, non-invasive bladder cancer, or treated in-situ cervical cancer). Prior lung cancer diagnosis now with oligometastatic recurrence is not an exclusion criteria.
• Patients with major activating mutations in EGFR (del19, L858R, and T790M) or ROS 1 or ALK gene rearrangements are excluded

Eligibility for Randomization

• Once enrolled on study, patients will have a PET/MRI brain for restaging. Patients with no evidence of progression and 8 or fewer sites of active persistent disease per the treating physician are eligible for randomization.
• If a PET has been performed within 30 days of enrollment with no evidence of progression per RECIST v1.1, then this scan may be used and does not have to be repeated prior to randomization.
• If an MRI brain has been performed within 90 days of enrollment with no evidence of progression per RECIST v1.1, then this scan may be used and does not have to be repeated prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab; 3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.	Radiation: Stereotactic Body Radiation Therapy; Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT); Other Names: Stereotactic Ablative Body Radiation Therapy; Biological: Pembrolizumab; Patients undergo 3-10 treatments of SBRT. Patients also receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475
Experimental: Arm 2 Pembrolizumab Only; Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.	Biological: Pembrolizumab; Patients undergo 3-10 treatments of SBRT. Patients also receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy	Will be determined using the product-limit method of Kaplan and Meier. Will compare unadjusted median PFS between the 2 arms using a log-rank test. Will also use a proportional hazards model to compare progression-free survival between the two groups, adjusting for key covariates such as age, performance (Eastern Cooperative Oncology Group) status, response to initial systemic therapy versus (vs) stable disease, the presence or absence of brain metastases, PD-L1 [programmed death-ligand ] expression (< 1% vs > 50%), tumor histology (adenocarcinoma vs non-adenocarcinoma), and number of disease sites treated (1-3 sites vs 4-6 sites). Progression is defined using RECIST v1.1 is relative Increase: A 20% increase in the sum of the longest diameters of target lesions (from baseline or nadir) is a criterion for PD.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Survival	Overall Survival is defined as the duration from the start of first line standard of care systemic therapy to the date of death or date of last contact; those lost to follow-up will be censored and will be reported with an exact 95% confidence interval.	Up to 5 years
Number of Participants With Progression	In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy.	Baseline up to 5 years
Number of Participants to Have a Rate of Failure	Investigators will assess the rate of failures inside and outside of radiation treatment.	Baseline up to 5 years
Number of Participants With New Sites of Disease	Investigators will assess the development of new sites of disease during or after immunotherapy	Baseline up to 5 years
Number of Participants With Adverse Events	All safety measures, including acute and late toxicity, will be reported using descriptive statistics (mean, median, standard deviation, proportions, and 95% confidence intervals). This will include calculating frequency/risk of adverse events by treatment site. Potential toxicities reported would include pneumonitis, esophagitis, chest wall pain, dermatologic toxicity, renal dysfunction, gastrointestinal toxicity including nausea, vomiting, and diarrhea, hepatotoxicity, and abdominal pain. These toxicities would be assessed according to site of irradiation by the treating physician and graded as per Common Terminology Criteria for Adverse Events 5.	Up to 5 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Farris, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2019
• Primary Completion (Actual): April 21, 2025
• Study Completion (Actual): April 21, 2025

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: IRB00056681; P30CA012197 (U.S. NIH Grant/Contract); NCI-2019-01259 (Other Identifier: Clinical Trial Reporting Program); CCCWFU 62718 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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