NCT03867175

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

Completed Phase 3 Results posted Last updated 13 June 2025

What this trial tests

Phase 3 trial testing Stereotactic Body Radiation Therapy in Metastatic Lung Cancer in 5 participants. Completed in 21 April 2025.

Timeline

24 June 2019

Primary endpoint
21 April 2025

21 April 2025

Quick facts

Lead sponsor	Wake Forest University Health Sciences
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	24 June 2019
Primary completion	21 April 2025
Estimated completion	21 April 2025
Sites	1 location across United States

Drugs / interventions tested

• Stereotactic Body Radiation Therapy — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Metastatic Lung Cancer — all drugs for Metastatic Lung Cancer →
• Stage IV Lung Cancer — all drugs for Stage IV Lung Cancer →

Sponsor

Wake Forest University Health Sciences

Who can join

18 and older, any sex, with Metastatic Lung Cancer or Stage IV Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy Primary · Up to 5 years

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 dise

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	1
Arm 2 Pembrolizumab Only	0

Number of Participants With Overall Survival Secondary · Up to 5 years

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.

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	1
Arm 2 Pembrolizumab Only	0

Number of Participants With Progression Secondary · Baseline up to 5 years

In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy.

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	1
Arm 2 Pembrolizumab Only	0

Number of Participants to Have a Rate of Failure Secondary · Baseline up to 5 years

Investigators will assess the rate of failures inside and outside of radiation treatment.

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	1
Arm 2 Pembrolizumab Only	0

Number of Participants With New Sites of Disease Secondary · Baseline up to 5 years

Investigators will assess the development of new sites of disease during or after immunotherapy

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	1
Arm 2 Pembrolizumab Only	0

Number of Participants With Adverse Events Secondary · Up to 5 years

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

Group	Value	95% CI
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab	4
Arm 2 Pembrolizumab Only	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 5 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab

Serious: 2/4 (50%)

Deaths: 1/4

Arm 2 Pembrolizumab Only

Serious: 1/1 (100%)

Deaths: 0/1

Serious adverse events (5 terms)

Reaction	System	Arm 1 Stereotactic Body Ra…	Arm 2 Pembrolizumab Only
Hypertension	Vascular disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Central nervous system necrosis	Nervous system disorders	—	—
Edema cerebral	Nervous system disorders	—	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (63 terms — click to expand)

Reaction	System	Arm 1 Stereotactic Body Ra…	Arm 2 Pembrolizumab Only
Anemia	Blood and lymphatic system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Hypertension	Vascular disorders	—	—
Lymphocyte count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Fatigue	General disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Bloating	Gastrointestinal disorders	—	—
Alkaline phosphatase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Platelet count decreased	Investigations	—	—
Sinus disorder	Respiratory, thoracic and mediastinal disorders	—	—
Thyroid stimulating hormone increased	Investigations	—	—
Chest wall pain	Musculoskeletal and connective tissue disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Paresthesia	Nervous system disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Sinusitis	Infections and infestations	—	—
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Dizziness	Nervous system disorders	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—
Shingles	Infections and infestations	—	—
Upper respiratory infection	Infections and infestations	—	—
Central nervous system necrosis	Nervous system disorders	—	—
Dry eye	Eye disorders	—	—
Edema cerebral	Nervous system disorders	—	—
Edema limbs	General disorders	—	—

Most-reported serious reactions: Hypertension, Lymphocyte count decreased, Central nervous system necrosis, Edema cerebral, Generalized muscle weakness.

Data from ClinicalTrials.gov NCT03867175 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Radiotherapy combined with immunotherapy: the dawn of cancer treatment.
   Zhang Z, Liu X, Chen D, Yu J. · · 2022 · cited 463× · PMID 35906199 · DOI 10.1038/s41392-022-01102-y
2. The emerging role of epigenetic therapeutics in immuno-oncology.
   Topper MJ, Vaz M, Marrone KA, Brahmer JR, et al · · 2020 · cited 331× · PMID 31548600 · DOI 10.1038/s41571-019-0266-5
3. Type I interferon-mediated tumor immunity and its role in immunotherapy.
   Yu R, Zhu B, Chen D. · · 2022 · cited 229× · PMID 35292881 · DOI 10.1007/s00018-022-04219-z
4. SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges.
   Chen Y, Gao M, Huang Z, Yu J, et al · · 2020 · cited 125× · PMID 32723363 · DOI 10.1186/s13045-020-00940-z
5. Tumour Hypoxia-Mediated Immunosuppression: Mechanisms and Therapeutic Approaches to Improve Cancer Immunotherapy.
   Fu Z, Mowday AM, Smaill JB, Hermans IF, et al · · 2021 · cited 86× · PMID 33923305 · DOI 10.3390/cells10051006
6. Immunotherapy of brain metastases: breaking a "dogma".
   Di Giacomo AM, Valente M, Cerase A, Lofiego MF, et al · · 2019 · cited 69× · PMID 31623643 · DOI 10.1186/s13046-019-1426-2
7. Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments.
   Procureur A, Simonaggio A, Bibault JE, Oudard S, et al · · 2021 · cited 49× · PMID 33567530 · DOI 10.3390/cancers13040678
8. The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.
   Low JL, Walsh RJ, Ang Y, Chan G, et al · · 2019 · cited 45× · PMID 31497071 · DOI 10.1177/1758835919870360