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

NCT03867175 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: IRB00056681NCI-2019-01259CCCWFU 62718P30CA012197
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Lung Cancer; Stage IV Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Participants With Overall Survival

  Up to 5 years

• Number of Participants With Progression

  Baseline up to 5 years

• Number of Participants to Have a Rate of Failure

  Baseline up to 5 years

• Number of Participants With New Sites of Disease

  Baseline up to 5 years

• Number of Participants With Adverse Events

  Up to 5 years

Study Arms (2)

Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

Arm 2 Pembrolizumab Only

EXPERIMENTAL

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

Biological: Pembrolizumab

Interventions

Stereotactic Body Radiation Therapy RADIATION

Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT)

Also known as: Stereotactic Ablative Body Radiation Therapy

Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab

Pembrolizumab BIOLOGICAL

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.

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab; Arm 2 Pembrolizumab Only

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• More than 180 days has elapsed since day 1 of cycle 1 of standard of care systemic therapy.
• Pregnant or lactating women.
• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Radiosurgery; pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

This study enrolled n=5 patients. Four of 5 were randomized to arm 1, and the remaining patient was randomized to arm 2. Only one patient (arm 1) had any primary/secondary outcomes--1 patient in arm 1 had progression to a new disease site and died soon thereafter. Due to these small numbers statistical analysis (e.g., rates, statistical comparisons of arms) are not possible. Descriptive and count data have thus been entered into the outcomes data fields.

Results Point of Contact

• Title: Principal Investigator
• Organization: Wake Forest Baptist Comprehensive Cancer Center

mfarris@wakehealth.edu

3367130031

Study Officials

• Michael Farris, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 7, 2019
• Study Start: June 24, 2019
• Primary Completion: April 21, 2025
• Study Completion: April 21, 2025
• Last Updated: June 13, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)