Pembrolizumab and Stereotactic Body Radiation Therapy in Treating Patients with Metastatic Melanoma or Non-small Cell Lung Cancer
- Be willing and able to provide written informed consent/assent for the trial
- Have metastatic melanoma or NSCLC, or locally advanced NSCLC not suitable for curative-intent local therapy
- For melanoma patients, patients must have received prior programmed cell death protein 1 (PD-1) therapy and have progressed immune-related progressive disease (irPD) by immune-related Response Criteria (irRC)
- Have 2 or more measurable sites of disease as defined by either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or cutaneous lesions at least 1 cm in greatest dimension
- Have at least one site of disease that is considered potentially suitable for treatment with SBRT
- Have provided tissue from an archival or newly obtained tissue sample of a tumor lesion, sufficient for analysis of programmed cell death 1 ligand 1 (PD-L1) and other biomarkers; patients who have had PD-L1 analysis previously performed at Merck can substitute earlier analysis results and are not required to submit additional tissue for PD-L1 testing; expression of PD-L1 is NOT required for study entry
- Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Absolute neutrophil count (ANC) >= 1,500 /mcL
- Platelets >= 100,000 /mcL
- Hemoglobin >= 9 g/dL
- Serum creatinine <= 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) <= 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- NSCLC patients who have received prior therapy with an agent directed at PD-1, PD-L1, or programmed cell death 1 ligand 2 (PD-L2)
- Has had systemic corticosteroids within 2 weeks of the first dose of protocol-related radiation or MK-3475
- Has had radiation therapy within 2 weeks of the first protocol treatment
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 2 weeks of the first protocol treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks of the first protocol treatment; the use of low-dose steroids for management of chronic conditions is allowed
- Non-small cell lung cancer patients only: has had a prior monoclonal antibody within 4 weeks prior to first protocol treatment or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of the first protocol treatment 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: Patients who have had prior treatments with tyrosine kinase inhibitors (e.g. Tarceva) require only a 72-hour washout period prior to starting protocol treatment
- Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Has known active and untreated brain (central nervous system [CNS]) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an example of an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; those with a history of hypothyroidism who are now stable on hormone replacement will not be excluded; those with Sjorgen’s syndrome will not be excluded from the study
- Has evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis
- Has an active infection requiring systemic therapy
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Has received a live vaccine within 30 days prior to the first protocol treatment
I. To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) to lung (Arm A) and non-lung (Arm B) targets in patients receiving pembrolizumab (MK-3475). (Phase Ib)
II. To determine the overall response rate to post-radiation MK-3475, in patients whose disease had previously progressed on MK-3475. (Phase IIa)
I. To determine the local control of SBRT, when SBRT is given with MK-3475.
II. To determine the time to progression in patients receiving post-radiation MK-3475, in patients whose disease had previously progressed on MK-3475.
III. To determine the progression-free and overall survival in patients MK-3475, who receive SBRT.
IV. To determine the safety and toxicity of the combination of SBRT and MK-3475.
V. To examine potential predictive biomarkers in tumor samples and peripheral blood in patients treated with MK-3475 and SBRT.
OUTLINE: This is a phase Ib, dose-escalation study of SBRT followed by a phase IIa study. Patients are assigned to 1 of 2 arms.
ARM A (NON-SMALL CELL LUNG CANGER [NSCLC]): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity. After progression of disease, patients undergo SBRT. Patients then receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity.
ARM B (MELANOMA): Patients undergo SBRT. Patients then receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 18 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
Trial Phase Phase I/II
Trial Type Treatment
Roy H. Decker
- Primary ID 1411014879
- Secondary IDs NCI-2016-00944
- Clinicaltrials.gov ID NCT02407171