Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer

Inclusion Criteria:

- Willingness and ability to provide written informed consent

- Willingness and ability to comply with required study visits and procedures

- For Biopsy Patients: Willingness to undergo repeat biopsy of tumor before and after
treatment

- Men or women ≥ 18 years of age.

- Histologically confirmed advanced solid tumor for which curative treatment is not
available.

- Have undergone appropriate standard of care treatment options (in the opinion of the
treating investigator). Participants with NSCLC must have undergone EGFR and ALK
testing and have received appropriate initial therapy.

- Measurable disease, including at least one tumor lesion that meets criteria for
multi-organ site ablative radiation therapy (MOSART) SBRT radiation.

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1

- Adequate organ function, as defined by the following:

- Absolute neutrophil count (ANC) ≥ 1,500/µL

- Platelets ≥ 100 x 10^3/µL

- Hemoglobin ≥ 8 g/dL without transfusion or EPO dependency

- Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) OR measured or
calculated creatinine clearance (CrCL) > 50 mL/min (creatinine clearance should be
calculated per institutional standard). GFR can also be used in place of creatinine of
CrCl.

- Serum total bilirubin ≤1.5 x institutional ULN (except subjects with Gilbert's
Syndrome, who must have normal direct bilirubin).

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x
institutional ULN OR ≤ 5x ULN for subjects with liver metastases.

- Albumin > 3.2 mg/dL.

- Prior immuno-oncology (IO) therapy

- Have a physician determined life expectancy of at least 6 months.

- Negative pregnancy test for women of childbearing potential (WOCBP) within 72 hours of
starting therapy

- Must not be breastfeeding

- Woman of childbearing potential: Must agree to follow instructions for method(s) of
contraception for the duration of treatment with study drug(s) and up to 5 months post
last dose of study drug(s).

- Men: Must agree to follow instructions for method(s) of contraception for the duration
of treatment with study drug(s) and up to 7 months post last dose of study drug(s).
Must be willing to refrain from sperm donation during this time.

Exclusion Criteria:

- Must not be currently receiving study therapy or have 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.

- Must not have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior
to study Day 1 or have not recovered (i.e. < grade 1 at baseline) from adverse events
due to agents administered more than 4 weeks earlier.

- Must not have had prior chemotherapy, targeted small molecule therapy, radiation or
other anti-cancer therapy (with exceptions for disease-specific hormone treatments
considered standard of care) within 2 weeks prior to study Day 1 or have not recovered
(i.e. < grade 1 or at baseline) from adverse events due to a previously administered
agent. Exception for ≤ grade 2 neuropathy. If patient received major surgery, they
must have recovered adequately from the toxicity and/or complications from the
intervention prior to starting therapy.

- Must not have known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Patients with previously treated brain metastases may
participate provided they are stable, have no evidence of new or enlarging brain
metastases, and are not using steroids for at least 7 days prior to trial treatment.

- Must not have had prior radiation therapy (defined as >10% of prior prescription dose)
to the area planning to be treated with SBRT.

- Must not have a diagnosis of immunodeficiency or is receiving systemic steroid therapy
at a dose of >10 mg prednisone daily or equivalent at time of first dose of trial
treatment.

- Must not have a known history of active TB (Bacillus Tuberculosis)

- Must not have hypersensitivity to nivolumab, urelumab, cabiralizumab or any of their
excipients.

- Must not have a known additional malignancy that could confuse analysis of on-study
treatment. Inclusion of all study participants with more than one malignancy must be
discussed and approved by the PI.

- Must not have 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
corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.

- Must not have a known history of non-infectious pneumonitis that required steroids for
treatment.

- Must not have evidence of interstitial lung disease.

- Must not have an active infection requiring systemic therapy.

- Must not have 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.

- 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.

- If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected) then patient is not eligible for cohorts including SBRT to
liver lesions.

- Participants must not have had prior organ allograft or allogeneic bone marrow
transplantation.

- Participants must not have had uncontrolled or significant cardiovascular disease
including, but not limited to, any of the following:

- Myocardial infarction or stroke/transient ischemic attack within the past 6
months

- Uncontrolled angina within the past 3 months

- Any history of clinically significant arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)

- History of other clinically significant heart disease (eg, cardiomyopathy,
congestive heart failure with New York Heart Association functional
classification III to IV, pericarditis, significant pericardial effusion, or
myocarditis)

- Cardiovascular disease-related requirement for daily supplemental oxygen therapy

- Has received a live vaccine within 30 days of planned start of study therapy.

- Participants may not concomitantly use statins while on study. However, a patient
using statins for over 3 months prior to study drug administration and in stable
status without CK rise may be permitted to enroll.

- Participants may not have current or history of clinically significant muscle
disorders (eg, myositis), recent unresolved muscle injury, or any condition known to
elevate serum CK levels.

- Must not have a history of allergy to nivolumab, urelumab or cabiralizumab.

- Must not have a history of any significant drug allergy (such as anaphylaxis or
hepatotoxicity) to prior anti-cancer immune-modulating therapies (eg, checkpoint
inhibitors and T-cell co-stimulatory antibodies).

- Must not be prisoners or be involuntarily incarcerated.

- Must not be compulsorily detained for treatment of either a psychiatric or physical
(eg, infectious disease) illness.