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

NCT02858869 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB00086461NCI-2016-00718RAD3179-16P30CA138292
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Mucosal Melanoma; Ocular Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Skin Melanoma; Melanoma of Unknown Primary

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities

  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 (%).

  3 months after first pembrolizumab dose

Secondary Outcomes (4)

• Overall Survival

  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

• Rate of Symptomatic Radiation Necrosis

  Up to 12 months after first pembrolizumab dose

• Clinical Benefit (Intra-cranial)

  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

• Clinical Benefit (Extra-cranial)

  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

Study Arms (3)

Arm A (pembrolizumab, SRS 6 Gy, CLOSED):

EXPERIMENTAL

Patients receive 200 mg pembrolizumab IV over 30 minutes on day 1. Courses repeat Q3W for at least 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo 5 SRS fractions between days 2-15 of course 1.

Biological: Pembrolizumab; Radiation: Stereotactic Radiosurgery

Arm B (pembrolizumab, SRS 9 Gy)

EXPERIMENTAL

Patients receive pembrolizumab IV as in Arm A. Patients undergo 3 SRS fractions between days 2-15 of course 1.

Biological: Pembrolizumab; Radiation: Stereotactic Radiosurgery

Arm C (pembrolizumab, SRS 18-21 Gy)

EXPERIMENTAL

Patients receive pembrolizumab IV as in Arm A. Patients undergo 1 SRS fraction between days 2-3 of course 1.

Biological: Pembrolizumab; Radiation: Stereotactic Radiosurgery

Interventions

Pembrolizumab BIOLOGICAL

Given IV

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

Arm A (pembrolizumab, SRS 6 Gy, CLOSED):; Arm B (pembrolizumab, SRS 9 Gy); Arm C (pembrolizumab, SRS 18-21 Gy)

Stereotactic Radiosurgery RADIATION

Undergo SRS

Also known as: Stereotactic External Beam Irradiation, Stereotactic External-Beam Radiation Therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, Stereotaxic Radiation Therapy, Stereotaxic Radiosurgery

Arm A (pembrolizumab, SRS 6 Gy, CLOSED):; Arm B (pembrolizumab, SRS 9 Gy); Arm C (pembrolizumab, SRS 18-21 Gy)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Eastern Cooperative Oncology Group (ECOG) performance scale (PS) of 0-1; Karnofsky performance status ≥ 70%
• Patients must have histological diagnosis of melanoma or non-small cell lung cancer (biopsy will be done per standard of care, if needed to prove metastatic melanoma and/or NSCLC as well as for clinically relevant mutation analysis); additional biopsy will be per standard of care
• Patients can be treated either in first line or in the refractory setting; programmed death-ligand 1 (PD-L1) positivity is not required for enrollment
• All melanoma patients may be tested for proto-oncogene B-Raf (BRAF) as part of routine standard of care, but is not a requirement for the trial; all NSCLC patients may be tested for with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as part of standard of care, but is not a requirement of the trial
• Having gotten prior programmed cell death protein 1 (PD1) therapy is allowed for, especially if they have previously progressed on it; progression may include extra-cranial as well as intra-cranial progression; after progressing on PD1 therapy, intervening chemotherapy and/or targeted therapy (BRAF inhibitors \[BRAFi\], etc) is allowed; if they are on intervening chemotherapy and/or targeted therapy (BRAFi, etc), they have to have progression intra-cranially and/or extra-cranially and must be off intervening therapy for at least 2 weeks
• Patient must be asymptomatic at time of getting SRS (day 0) on trial; prednisone \< 10 mg/day for at least 7 days prior to treatment is allowed
• Patients with ocular, mucosal and unknown primary melanoma will also be eligible
• Patients with 1-10 untreated brain metastases at time of initial brain metastases diagnosis (surgery to one of the brain lesions and/or biopsy of a lesion for diagnostic purposes and/or for standard of care purposes is acceptable)
• Largest brain metastases volume measures less than 14.15 cc³
• Prior radiation to the primary and/or regional radiotherapy for melanoma and/or NSCLC is acceptable
• Baseline labs as within standard of care (complete blood count \[CBC\], basic metabolic panel \[BMP\], lactate dehydrogenase \[LDH\], erythrocyte sedimentation rate \[ESR\], etc) are required within 14 days of enrollment
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients must have at least 14 days to recover from all prior treatment, including surgery, chemotherapy, immunotherapies, prior to enrollment on this protocol
• Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• If they have brain metastases located in the brain stem (including midbrain, pons, or medulla)
• Inability to undergo magnetic resonance imaging (MRI) evaluation for treatment planning and follow-up
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its recipients
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Melanoma; Uveal Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mohammad K Khan
• Organization: Emory University

m.k.khan@emory.edu

404-778-3473

Study Officials

• Mohammad K. Khan, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: August 8, 2016
• Study Start: October 4, 2016
• Primary Completion: November 19, 2020
• Study Completion: October 28, 2023
• Last Updated: March 9, 2026
• Results First Posted: March 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)