CBL0137 in Treating Patients With Advanced Extremity Melanoma or Sarcoma

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and examine the dose-limiting toxicities of
intra-arterial facilitates chromatin transcription (FACT) complex-targeting curaxin CBL0137
(CBL0137) in patients with advanced extremity melanoma or sarcoma.

SECONDARY OBJECTIVES:

I. To assess the tumor response in advanced melanoma and sarcoma patients treated with
intra-arterial administration of CBL0137.

II. To define both response in-field (area of the limb distal to the infusion point) and
out-of-field (any area proximal to the infusion point) in patients treated with CBL0137 based
intra-arterial infusion.

III. Assess the pharmacokinetics of CBL0137 in the study population pre-and post CBL0137
intraarterial infusion.

IV. Assess tumor protein expression profiles before and after treatment with CBL0137.

TERTIARY OBJECTIVES:

I. To assess if the proposed treatment has any effect on quality of life as measured by the
Functional Assessment of Cancer Therapy ? Melanoma (assessment tool also applicable to
sarcoma).

OUTLINE: This is a dose-escalation study of FACT complex-targeting curaxin CBL0137.

Patients receive FACT complex-targeting curaxin CBL0137 intra-arterially (IA) over 15
minutes.

After completion of study treatment, patients are followed up at 2, 6 and 12 weeks, every 3
months for 12 months, then at 24 months.

Inclusion Criteria:

- Patient must have a life expectancy of > 6 months.

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

- Patients either:

- Must not have undergone any limb-directed treatment.

- Have undergone a previous Melphalan based regional therapy for which they did not
respond optimally and, present with persistent, progressive, or recurrent
disease.

- Patient must have had a washout period for at least 30 days or 5 half-lives from any
prior chemotherapy, radioactive or hormonal cancer therapy, or 4 weeks from any
checkpoint inhibitors or other biologic, whichever is longer.

- NOTE: Patients with indeterminate staging must be reviewed by the Principal
Investigator prior to registration.

- Patient must have histologically proven primary or recurrent extremity melanoma (stage
IIIB, IIIC, or IV), or advanced extremity sarcoma not amenable to surgical resection
(American Joint Committee on Cancer [AJCC] staging must be documented in patient's
medical record, as determined by computed tomography [CT] of the chest, abdomen and
pelvis, and/or whole body positron emission tomography [PET] scan, within six weeks
prior to administration of study drug).

- Patients with Stage IIIC disease must either have had regional lymph nodes previously
removed or have stable or regressed disease on imaging from prior systemic therapy
(defined as RECIST 1.1 SD, CR, or PR). Stable or regressed disease must be present for
at least the 2 months prior to IA CBL0137 and patient is no longer receiving systemic
therapy during this time period..

- Patients with Stage IV disease must have had all distant disease resected at least 30
days prior to regional treatment, or exhibit stable or regressed disease .on imaging
from prior systemic therapy (defined as RECIST 1.1 SD, CR, or PR). Stable or regressed
disease must be present for at least the 2 months prior to IA CBL0137 and patient is
no longer receiving systemic therapy during this time period.

- Melanoma patients who have stable or completely responded brain metastases from
previous gamma knife surgery and/or systemic therapies are eligible.

- Patient's disease must be measured by caliper or radiological method as defined in the
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

- Hemoglobin >= 9 g/dL.

- White blood count (WBC) of >= 3000 m^3.

- Absolute neutrophil count (ANC) >= 1,500/mm^3.

- Platelet count >= 100,000/mm^3.

- Total bilirubin =< 1.5 x upper limit of normal (ULN).

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x the ULN.

- Creatinine clearance (CrCl) > 45 mL/minute.

- Patient must have a palpable femoral/radial pulse in the affected extremity.

- Recovery from relevant toxicity prior to first study drug administration.

- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
entry. Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately.

- Ability to read and understand English and the ability to complete paper and/or
electronic survey assessments.

- Participant or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure.

Exclusion Criteria:

- Cardiac disease: Congestive heart failure > Class II New York Heart Association
(NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset
angina (began within the last 3 months) or myocardial infarction within the past 6
months

- Males with mean QTcF values of >450 msec and females with QTcF values of >470 msec,
patients who are known to have congenital prolonged QT syndromes, or patients who are
on medications known to cause prolonged QT intervals on ECG.

- Use of drugs known to prolong QT.

- Patients with known hypersensitivity to any of the components of CBL0137.

- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

- Thrombotic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

- Patients with symptoms or signs of vascular insufficiency. Specifically, patients with
any history of blood clots or lifestyle altering ischemic peripheral vascular disease
will be excluded.

- Evidence or history of bleeding diathesis or coagulopathy.

- Patients with known heparin induced thrombocytopenia.

- Untreated or growing brain metastasis: Patients with neurological symptoms must
undergo a CT scan/magnetic resonance imaging (MRI) of the brain to exclude untreated
or growing brain metastasis.

- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.

- Active clinically serious infection > Common Terminology Criteria for Adverse Events
(CTCAE) Grade 2.

- Serious non-healing wound, ulcer, or bone fracture.

- Major surgery or significant traumatic injury within 30 days of planned intra-arterial
infusion.

- Current treatment or, treatment within the previous 24 months, for another
non-melanoma or sarcoma malignancy.

- Patients who have already received 2 prior infusions of CBL0137.

- Pregnant or nursing female participants.

- Psychiatric conditions or diminished capacity that could compromise the giving of
informed consent, or interfere with study compliance.

- Unwilling or unable to follow protocol requirements.

- Any condition which in the Investigator?s opinion deems the participant an unsuitable
candidate to receive study drug.

- Received an investigational agent within 30 days prior to enrollment.