Liver SBRT in Combination With Immune Checkpoint Inhibition in Patients With Metastatic Non-small Cell Lung Cancer

Recruitment & Eligibility

Inclusion Criteria

Adult patients (≥18 years of age)
Histologically or cytologically confirmed NSCLC with liver metastases
Eligible for immune checkpoint inhibitors per treating medical oncologist
Disease must be measurable per RECIST criteria
ECOG Performance status of 0 - 2
Adequate organ function per protocol.
Allowable prior therapy includes adjuvant durvalumab, prior radiotherapy outside the upper abdomen.
Patients must be willing and able to sign an informed consent form.
Participants of childbearing potential willing to undergo pregnancy test and use contraception per Appendix.

Exclusion Criteria

Liver tumor burden which cannot be targeted with SBRT per treating radiation oncologist
Presence of uncontrolled intercurrent illness or significant comorbidities precluding participation in a clinical study as determined by investigator
Diagnosis of underlying parenchymal end stage liver disease (cirrhosis) or biliary disease (primary biliary cirrhosis).
Other invasive malignancy active within 1 years, excluding in situ cancers
Presence of psychiatric or substance abuse disorders that would interfere with compliance or safety
Has a known history of active Bacillus Tuberculosis (TB), Hepatitis B or Hepatitis C infection
Has received a live (active) vaccine within 30 days of enrollment.
Active autoimmune disease that has required systemic treatment in the past 1 years aside from hormone replacement therapy (ie. thyroxine, insulin, or physiologic corticosteroid replacement therapy)
Baseline corticosteroid use (>10 mg prednisone daily or equivalent) at study entry
Pregnancy or breast feeding

Study & Design

Arm && Interventions

Group	Intervention	Description
Arm 1	Liver SBRT	This is an open-label, single-arm, single center clinical trial to evaluate the feasibility of liver SBRT (up to 4 metastases) during the first cycle of physician's choice ICI for NSCLC.
Arm 1	Pembrolizumab	This is an open-label, single-arm, single center clinical trial to evaluate the feasibility of liver SBRT (up to 4 metastases) during the first cycle of physician's choice ICI for NSCLC.

Primary Outcome Measures

Name	Time	Method
Percentage of patients who receive all fractions of radiotherapy as planned	Up to 0.5 years after start of study treatment	Feasibility determination. Analyzed with descriptive statistics.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients who develop grade 3 or higher toxicity	Up to 1 year after start of study treatment	Any serious adverse event that occurs within 60 days after treatment with SBRT or after this time frame and is considered related to the study treatment will also be reported. Analyzed with descriptive statistics.
Progression-free survival	Time Frame: Up to 3 years after end of study treatment	PFS defined as the time from start of treatment to date of radiological or clinical progression (leading to withdrawal from the study), or death from any cause, whichever comes first. Assessed Per RECIST v1.1; analyzed using Kaplan-Meier curves and descriptive statistics.
Overall survival (OS)	Time Frame: Up to 3 years after end of study treatment	OS defined as the time from start of treatment to death. This will be analyzed using Kaplan-Meier curves and descriptive statistics.
Proportion of patients with local control	Time Frame: Up to 3 years after end of study treatment	Freedom from local progression (local control) is defined as the lack of progression of the tumors treated by RT, either by tumor size or enhancement. Progression or development of new tumors elsewhere in the liver or outside of the liver would not constitute a local control failure. Tumors which increase in size or demonstrate new or increasing enhancement are considered progression. Analyzed using Kaplan-Meier curves and descriptive statistics.

Recruitment & Eligibility