This is an open-label, historically controlled pilot study investigating the immune effect of
Laser Interstitial ThermotHerapy (LITT)+ pembrolizumab in patients with melanoma, non-small
cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) brain metastases that recur after
prior stereotactic radiosurgery (SRS).
Adult patients with a primary cancer approved by the FDA for treatment with an
immune-checkpoint inhibitor who have recurrent brain metastasis that have failed stereotactic
radiosurgery treatment will be screened. They will sign consent and complete screening
procedures. Each patient will be scheduled to undergo biopsy and LITT treatment. Within two
weeks of surgery, patients will begin receiving pembrolizumab every three weeks.
Pembrolizumab infusions will continue until brain met recurrence per RANO for Brain Mets or
up to two years, whichever comes first. Blood samples will be collected for immune
monitoring. Tumor tissue will be collected for immune and genomic studies. Approximately 21
patients will be enrolled to accrue 15 evaluable subjects. Patients will be followed for
survival data for one year or until death, whichever comes first.
1. Histologic confirmation of primary cancer approved by the FDA for treatment with an
immune-checkpoint inhibitor, generally:
2. Non-Small Cell Lung Cancer
3. Small Cell Lung Cancer
4. Head and Neck Squamous Cell Cancer
5. Classical Hodgkin Lymphoma
6. Primary Mediastinal Large B-Cell Lymphoma
7. Urothelial Carcinoma
8. Microsatellite Instability-High Cancer
9. Gastric Cancer
10. Esophageal Cancer
11. Cervical Cancer
12. Hepatocellular Carcinoma
13. Merkel Cell Carcinoma
14. Renal Cell Carcinoma
2. At least one metastatic lesion has had prior SRS. Each patient's scan must be reviewed
by a neurosurgeon or radiation oncologist prior to enrollment.
3. KPS ≥ 70.
4. 18 years or older.
5. Adequate bone marrow and organ function as defined below:
1. ANC ≥ 1,500/mcL
2. Platelets ≥ 100,000/mcL
3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)
4. Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60
mL/min for patients with serum creatinine > 1.5 x IULN
5. Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with
i) 1.5 x IULN f) AST (SGOT) and ALT (SGPT) ≤ 3 x IULN
6. Candidate for pembrolizumab treatment.
7. Candidate for LITT treatment:
1. Metastatic lesions individually measuring 3.5 cm or less
2. Only lesions that are growing or new will be treated with LITT
3. Five (5) or less target metastatic lesions that are new or growing
4. Lesions accessible with a laser probe as determined by the neurosurgeon
performing the procedure
5. Patient able to undergo MRI scans (no incompatible MRI hardware, etc.)
8. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively,
within 30 days prior to study enrollment.
9. Participants of childbearing age must use effective contraception:
a) Women of childbearing potential (WOCBP) must be using a highly effective method of
contraception to avoid pregnancy throughout the study and for at least 24 weeks after
the last dose of study drug to minimize the risk of pregnancy. Prior to study
enrollment, women of childbearing potential must be advised of the importance of
avoiding pregnancy during trial participation and the potential risk factors for an
unintentional pregnancy. Refer to Section 9.3 for guidance on highly effective
i) WOCBP include any woman who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation or
oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
(1) Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or (2)
For women with irregular menstrual periods who are taking hormone replacement therapy
(HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35
b) Males with female partners of childbearing potential must agree to use
physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout
the study and should avoid conceiving children for 24 weeks following the last dose of
10. Ability of the patient to understand and willingness to sign an IRB approved written
informed consent document.
11. Steroid dose equivalent to dexamethasone dose of ≤ 6mg daily at the time of enrollment.
1. Actively participating in another clinical trial on active study treatment; follow-up
or observational status is acceptable if more than 2 weeks since last study treatment.
2. History of immunodeficiency or is receiving any form of immunosuppressive therapy
within 7 days prior to the first dose of trial treatment (with the exception of daily
dexamethasone ≤ 6 mg).
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that
would limit compliance with study requirements.
4. History of active autoimmune disease requiring systemic treatment within 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.
5. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
6. Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy
test at screening.
7. Females or males of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period and for at least 24
weeks after the last dose of study drug.
8. Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
[qualitative] is detected) infection.
9. Known history of active TB (bacillus tuberculosis).
10. Known history of HIV (HIV 1/2 antibodies).