SD-101 and BMS-986178 in Treating Patients With Advanced or Metastatic Solid Malignancies

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of intratumoral TLR9 agonist SD-101 (SD-101) in
combination with intratumoral and intravenous anti-OX40 antibody BMS 986178 (BMS-986178) in
patients with advanced solid tumors.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of treatment with intratumoral SD 101 in combination with
intratumoral and intravenous BMS 986178 in patients with advanced solid tumors.

II. To evaluate changes in pharmacodynamic endpoints in serial tumor biopsies from intratumor
treated and untreated sites of disease.

OUTLINE:

SAFETY COHORT: Patients receive TLR9 agonist SD-101 intratumorally (IT) on days 1, 8 and 15.
Patients also receive anti-OX40 antibody BMS 986178 IT on days 8 and 15, and intravenously
(IV) over 30 minutes on days 8, 29 and 58.

EXPANSION COHORT: Patients receive TLR9 agonist SD-101 IT on days 1, 8 and 15. Patients also
receive anti-OX40 antibody BMS 986178 IT on days 1, 8 and 15, and IV over 30 minutes on days
1, 29 and 58.

After completion of study treatment, patients are followed up every 3-6 months.

Inclusion Criteria:

- Any advanced/metastatic, non-hematological, extracranial solid tumor malignancy with
disease progression after at least one line of standard therapy or for which standard
therapy known to prolong survival does not exist

- Patients must have at least two sites of disease that are >= 10 mm in diameter, one of
which must be accessible for intratumoral injection and core biopsies and the other of
which must be accessible for core biopsies by interventional radiology. (Sites have to
be deemed safe for repeated access upon IR review, based on anatomic location, size,
shape, and accessibility). Liver lesions may not be used as the injection site even if
otherwise deemed safe for access

- Patients must have at least one additional site of measurable disease by Response
Evaluation Criteria in Solid Tumors (RECIST) criteria, other than the sites selected
for intratumoral injection and core biopsies

- All patients with tumor types for which anti-PD-1 or anti PD-L1 therapy has been
approved should have received such therapy prior to enrollment, with evidence of
progression on at least two scans (ie, with pseudoprogression ruled out). Patients
with validated driver mutations should have received and progressed on appropriate
targeted therapy

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy of at least three months

- Total bilirubin < 1.5 x upper limit of normal (ULN) (unless patient has history of
Gilbert?s disease)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit
of normal (ULN)

- Creatinine < 1.5 x ULN or measured or calculated creatinine clearance (glomerular
filtration rate [GFR] can also be used in place of creatinine or creatinine [CrCl]) >=
60 mL/min for subject with creatinine levels > 1.5 x ULN

- Absolute neutrophil count (ANC) >= 1,500/mcL

- Hemoglobin >= 9 g/dL without transfusion within the past 4 weeks

- Platelets >= 100,000/mcL

- Prothrombin time (PT)/international normalized ratio (lNR) within normal limits

- Written informed consent obtained from subject

- Patients who have previously received an immune checkpoint inhibitor prior to
enrollment must have any immune related toxicities resolved to =< grade 1 or baseline
(prior to the checkpoint inhibitor) to be eligible. Patients who developed endocrine
adverse events on checkpoint inhibitor are eligible to enter regardless of the Common
Terminology Criteria for Adverse Events (CTCAE) Grade resolution as long as the
patient is well controlled on endocrine replacement

- Women of childbearing potential must have a urine or serum pregnancy test within 24
hours prior to the first dose of trial treatment. If the urine test is positive or
cannot be confirmed as negative, then a serum test will need to be negative

- Women of childbearing potential must practice a highly effective method of birth
control during treatment and for 160 days after treatment completion. Women of
childbearing potential who chose complete abstinence must agree to have a urine or
serum pregnancy tests within 24h of each dose of study treatment. If the urine test is
positive or cannot be confirmed as negative, then a serum test will need to be
negative

- Men who are sexually active with women of childbearing potential must agree to follow
instructions for methods of contraception while being treated on the study, and for
165 days after treatment completion. Men must agree to not donate sperm during this
time period

Exclusion Criteria:

- History of grade 2 or higher hypersensitivity reaction to either SD-101 or BMS-986178

- Patients who require immediate treatment or cytoreduction, as deemed by their
physician or the study investigators

- Treatment with other anticancer therapy (chemotherapy, small molecule, or radiation
therapy) within the past 3 weeks prior to study entry or within the past 6 weeks prior
to study entry for immunotherapies

- Use of investigational agent within the past 3 weeks prior to study enrollment

- Major surgery within 4 weeks of enrollment, or a wound that has not fully healed

- Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

- Symptomatic central nervous system (CNS) metastases

- Known bleeding disorder that is deemed to place the patient at unacceptable risk for
bleeding complications from intratumoral injection. Patients on anticoagulants and
anti-platelet agents other than aspirin are excluded

- Any uncontrolled bacterial, fungal, viral, or other infection

- Active autoimmune disease requiring systemic treatment within the past 2 years, with
the exception of patients well controlled on physiologic endocrine replacement

- Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other
immune suppressive drugs within 14 days prior to initiation of study drug. Steroids
for topical ophthalmic, inhaled, or nasal administration are allowed. Patients
requiring courses of systemic steroids for 14 consecutive days or less for an acute
condition (not for a chronic autoimmune illness) may receive study drug 14 days after
steroid therapy

- Patients with a history of other prior malignancy with the exception of non-melanoma
skin cancer, carcinoma in situ of the cervix, in situ carcinoma of the bladder, or
other malignancy that has undergone potentially curative therapy with no evidence of
disease for the last > 2 years and is deemed by the investigator to be a low risk for
recurrence

- Significant cardiac disease (New York Heart Association [NYHA] class IV congestive
heart failure, or unstable angina or myocardial infarction within the past 6 months)

- Human immunodeficiency virus (HIV) positive (+) patients or patients with active
hepatitis B or C infection

- Patients who are pregnant or breastfeeding

- Any other medical history, including laboratory results, deemed by the investigator
likely to interfere with their participation in the study, or to interfere with the
interpretation of the results