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NCT02858869

Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases

Completed Phase 1 Results posted Last updated 9 March 2026
What this trial tests

Phase 1 trial testing Pembrolizumab in Metastatic Malignant Neoplasm in the Brain in 25 participants. Completed in 28 October 2023.

Timeline
4 October 2016
Primary endpoint
19 November 2020
28 October 2023

Quick facts

Lead sponsorEmory University
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment25
Start date4 October 2016
Primary completion19 November 2020
Estimated completion28 October 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Emory University

Who can join

18 and older, any sex, with Metastatic Malignant Neoplasm in the Brain or Metastatic Melanoma. 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.

Dose Limiting Toxicities Primary · 3 months after first pembrolizumab dose

Number of dose limiting toxicity events defined as Radiation Therapy Oncology Group grade 3 central nervous system toxicities which are irreversible severe neurological symptoms requiring medications. Toxicity events for each arm will be reported, and 95% confidence intervals will be estimated using the Clopper-Pearson method. Number of with DLT (%).

GroupValue95% CI
Experimental: Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions)00 – 46
Experimental: Arm B (Pembrolizumab, 27 Gy Over 3 Fractions)00 – 26
Experimental: Arm C (Pembrolizumab, 18-21 Gy in One Fraction)00 – 41
Overall Survival Secondary · From first treatment on cycle 1, day 1 to the earlier of date of death and/or last follow up, assessed up to 3 years

Time from treatment initiation to death from any cause. Those who were alive were censored at last follow-up. Estimated using the Kaplan-Meier product-limit method. Median and 95% CI using Brookmeyer-Crowley method reported.

GroupValue95% CI
Experimental: Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions)NA0.99 – NA
Experimental: Arm B (Pembrolizumab, 27 Gy Over 3 Fractions)32.84.89 – NA
Experimental: Arm C (Pembrolizumab, 18-21 Gy in One Fraction)12.22.86 – NA
Rate of Symptomatic Radiation Necrosis Secondary · Up to 12 months after first pembrolizumab dose

Defined as proportion with evidence of necrosis on MRI images (radiographic evidence or radionecrosis) and a patient having neurological symptoms attributed to the location where the radiosurgery was done. The proportion will be reported, and a 95% confidence interval will be estimated using the Clopper-Pearson method. Number with symptomatic radiation necrosis.

GroupValue95% CI
Arm A (Pembrolizumab, SRS 6 Gy, CLOSED):00 – 46
Arm B (Pembrolizumab, SRS 9 Gy)16.72.1 – 48
Arm C (Pembrolizumab, SRS 18-21 Gy)14.30.3 – 58
Clinical Benefit (Intra-cranial) Secondary · From the first treatment on cycle 1, day 1 to the earlier of the recurrence event and/or last follow up/death, at least 6 months

Defined as proportion with a best overall response of stable disease or better for intracranial lesions present at baseline. Assessed using RECIST and immune RECIST Criteria. The proportion will be reported, and a 95% confidence interval will be estimated using the Clopper-Pearson method. Number with clinical benefit (%).

GroupValue95% CI
Experimental: Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions)10048 – 100
Experimental: Arm B (Pembrolizumab, 27 Gy Over 3 Fractions)6026 – 88
Experimental: Arm C (Pembrolizumab, 18-21 Gy in One Fraction)200.5 – 72
Clinical Benefit (Extra-cranial) Secondary · From the first treatment on cycle 1, day 1 to the earlier of the recurrence event and/or last follow up/death, at least 6 months

Defined as proportion with a best overall response of stable disease or better for extra-cranial lesions present at baseline. Assessed using RECIST and immune RECIST Criteria. Assessed using RECIST and immune RECIST Criteria. The proportion will be reported, and a 95% confidence interval will be estimated using the Clopper-Pearson method. Number with clinical benefit (%).

GroupValue95% CI
Experimental: Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions)6015 – 95
Experimental: Arm B (Pembrolizumab, 27 Gy Over 3 Fractions)5523 – 83
Experimental: Arm C (Pembrolizumab, 18-21 Gy in One Fraction)334 – 78

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious and Other Adverse Events assessed for 15 months, mortality assessed up to 3 years). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental: Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions)
Serious: 2/6 (33%)
Deaths: 3/6
Experimental: Arm B (Pembrolizumab, 27 Gy Over 3 Fractions)
Serious: 5/12 (42%)
Deaths: 7/12
Experimental: Arm C (Pembrolizumab, 18-21 Gy in One Fraction)
Serious: 1/7 (14%)
Deaths: 5/7

Serious adverse events (19 terms)

ReactionSystemExperimental: Arm A (Pembr…Experimental: Arm B (Pembr…Experimental: Arm C (Pembr…
Respiratory, thoracic and mediastinal disorders - Other, specify - Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
PalpitationsCardiac disorders
Non-cardiac chest painGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pleuritic painRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
FatigueGeneral disorders
FeverGeneral disorders
Abdominal painGastrointestinal disorders
Wound InfectionGeneral disorders
Chest Wall PainMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
shortness of breathGeneral disorders
Wound InfectionInfections and infestations
Other adverse events (15 terms — click to expand)

ReactionSystemExperimental: Arm A (Pembr…Experimental: Arm B (Pembr…Experimental: Arm C (Pembr…
HeadacheNervous system disorders
Symptomatic radionecrosisNervous system disorders
Extremity NumbnessNervous system disorders
Periorbital edemaEye disorders
DiarrheaGastrointestinal disorders
ConstipationGastrointestinal disorders
PainGeneral disorders
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
HypoglycemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
AgitationPsychiatric disorders
Radiation dermatitisSkin and subcutaneous tissue disorders
Dermatitis, otherSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Respiratory, thoracic and mediastinal disorders - Other, specify - Pulmonary embolism, Respiratory failure, Palpitations, Non-cardiac chest pain, Cough, Dyspnea, Pleural effusion, Pleuritic pain.

Data from ClinicalTrials.gov NCT02858869 adverse events section.

Sponsor's own description

This pilot trial studies the side effects of giving pembrolizumab together with stereotactic radiosurgery to treat patients with melanoma or non-small cell lung cancer that has spread to the brain. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Giving pembrolizumab together with stereotactic radiosurgery may be a better treatment for patients with melanoma or non-small cell lung cancer that has spread to the brain.

Publications & conference data

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

  1. Melanoma Management: From Epidemiology to Treatment and Latest Advances.
    Lopes J, Rodrigues CMP, Gaspar MM, Reis CP. · · 2022 · cited 98× · PMID 36230575 · DOI 10.3390/cancers14194652
  2. 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
  3. The Long-Term and Short-Term Efficacy of Immunotherapy in Non-Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Meta-Analysis.
    Chu X, Niu L, Xiao G, Peng H, et al · · 2022 · cited 46× · PMID 35693805 · DOI 10.3389/fimmu.2022.875488
  4. Stereotactic Radiosurgery and Immune Checkpoint Inhibitors in the Management of Brain Metastases.
    Lehrer EJ, McGee HM, Peterson JL, Vallow L, et al · · 2018 · cited 43× · PMID 30301252 · DOI 10.3390/ijms19103054
  5. Emerging principles of brain immunology and immune checkpoint blockade in brain metastases.
    Fares J, Ulasov I, Timashev P, Lesniak MS. · · 2021 · cited 40× · PMID 33893488 · DOI 10.1093/brain/awab012
  6. Brain metastases: An update on the multi-disciplinary approach of clinical management.
    Mitchell DK, Kwon HJ, Kubica PA, Huff WX, et al · · 2022 · cited 39× · PMID 33864773 · DOI 10.1016/j.neuchi.2021.04.001
  7. Melanoma Brain Metastases: Current Areas of Investigation and Future Directions.
    Glitza Oliva I, Tawbi H, Davies MA. · · 2017 · cited 39× · PMID 28114258 · DOI 10.1097/ppo.0000000000000237
  8. Tumor microenvironment in lung cancer-derived brain metastasis.
    Liu W, Powell CA, Wang Q. · · 2022 · cited 37× · PMID 35838548 · DOI 10.1097/cm9.0000000000002127

Verify or expand the search:

Other trials of Pembrolizumab

Trials testing the same drug.

Other recruiting trials for Metastatic Malignant Neoplasm in the Brain

Currently open trials in the same condition.

Other Emory University trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02858869.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing