Inclusion Criteria:
1. Written Informed Consent and HIPAA Authorization. 1. Subjects must have the nature of the study explained to them.
2. Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory tests, pharmacokinetic collections, and other requirements
of the study.
3. Subjects must provide a signed and dated IRB/IEC approved written informed
consent form (ICF) in accordance with regulatory and institutional guidelines.
4. Subjects must provide a signed and dated Health Insurance Portability and
Accountability Act (HIPAA) authorization.
5. The ICF and HIPAA authorization must be obtained before conducting any
procedures that do not form a part of the subject's normal care.
6. After signing the ICF and HIPAA Authorization, subjects will be evaluated for
study eligibility during the Screening Period (no more than 28 days before
study drug administration) according to the following further
inclusion/
exclusion criteria:
2. Target Population. 1. Histologically confirmed unresectable Stage III or Stage IV melanoma as per
AJCC staging system. (mucosal melanoma is acceptable).
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Prior disease progression on anti-PD1 therapy (i.e., anti-PD1 or anti-PD-L1,
including prior adjuvant). Prior anti-PD1 therapy must have been completed
prior to first dose of SX-682, and all adverse events related to prior therapy
have either returned to baseline or stabilized (other than endocrine toxicity
for which medical replacement therapy is in place).
4. Must have at least measurable non-CNS disease with at least 1 unidimensional
measurable lesion per RECIST v1.1.
5. Pre-treatment tumor tissue (i.e., archived paraffin-embedded) obtained in the
metastatic setting or from an unresectable site of disease must be available
for biomarker analyses. Biopsy should be excisional, incisional punch or core
needle. Fine needle aspirates or other cytology samples are insufficient.
6. Prior radiotherapy must have been completed at least 2 weeks prior to study
drug administration.
7. Screening laboratory values must meet the following criteria and should be
obtained within 14 days prior to first dose:
WBC > 3000/µL Neutrophils > 1500/ µL Platelets > 100,000/µL Hemoglobin > 9.0
g/dL (may have been transfused) Creatinine < 1.5 mg/dL AST/ALT < 2.5 X ULN for
subject with no liver metastases < 5 X ULN for subjects with liver metastases
Bilirubin < 1.5 mg/dL (unless diagnosed with Gilbert's syndrome, who can have
total bilirubin < 3.0 mg/dL) INR or PT < 1.5 X ULN unless the subject is
receiving anticoagulant therapy aPTT or PTT < 1.5 X ULN unless the subject is
receiving anticoagulant therapy. 8. Calculate and record creatinine clearance using the Cockcroft-Gault formula.
9. No known positivity for human immunodeficiency virus (HIV) (no laboratory
testing is required), no active infection with Hepatitis B or Hepatitis C.
10. Life expectancy > 12 weeks.
11. Subject Re-enrollment: This study permits the re-enrollment of a subject that
has discontinued the study as a pre-treatment failure (i.e., subject has not
been treated with SX-682) after obtaining agreement from the medical monitor
prior to re-enrolling a subject. If re-enrolled, the subject must be
re-consented.
3. Age and Reproductive Status. 1. Men and women, ages > 18 years of age.
2. Women of childbearing potential (WOCBP) must use method(s) of contraception (as
will be explained in detail) while on study and for 4 months after the last
dose of SX-682 or pembrolizumab. A WOCBP is defined as any female who has
experienced menarche and who has not undergone surgical sterilization
(hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is
defined clinically as 12 months of amenorrhea in a woman over age 45 in the
absence of other biological or physiological causes.
3. Women under the age of 62 with a history of being postmenopausal must have a
documented serum follicle stimulating hormone, (FSH) level > 40 mIU/mL.
4. Women must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study
drug.
5. Women must not be breastfeeding.
6. Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year while on study and for a period at least
6 months after the last dose of study drug.
7. Women who are not of childbearing potential and azoospermic men do not require
contraception.
Exclusion Criteria:
1. Target Disease Exceptions. 1. Active brain metastases or leptomeningeal metastases are eligible if the
treating physician determines that immediate CNS specific treatment is unlikely
to be required before trial screening/enrollment. Subjects with treated/stable
brain metastases are also eligible. An MRI is not required to rule out brain
metastases or leptomeningeal metastases. There must also be no requirement for
high doses of systemic corticosteroids that could result in immunosuppression
(> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug
administration.
2. Ocular melanoma is excluded (mucosal melanoma is acceptable).
2. Medical History and Concurrent Diseases. a) Any serious or uncontrolled medical disorder that, in the opinion of the
investigator, may increase the risk associated with study participation or study
drug administration, impair the ability of the subject to receive protocol therapy,
or interfere with the interpretation of study results. Specifically:
1. Subjects with active, non-infectious pneumonitis.
2. Subjects with interstitial lung disease or a history of pneumonitis that
required oral or intravenous glucocorticoids to assist with management.
3. Subjects with clinically significant heart disease that affects normal
activities.
b) Prior malignancy active within the previous 3 years except for locally curable
cancers that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
c) Subjects with active, known or suspected autoimmune disease. Subjects with
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
condition only requiring hormone replacement, psoriasis not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger
are permitted to enroll.
d) Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days of study drug administration. Inhaled or topical
steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are
permitted in the absence of active autoimmune disease.
e) Use of other investigational drugs (drugs not marketed for any indication) within
30 days before study drug administration.
f) Use of QT prolonging drugs (per their approved label) must be stopped at least
two
- (2) weeks before the start of SX-682 dosing and suspended for the length of the
trial, unless in the judgment of the investigator an alternative non-prolonging
substitute cannot be found, and the drug is absolutely medically necessary (if
applicable contact Syntrix medical monitor for further guidance on enhanced ECG
monitoring).
g) Subjects who have had major surgery in the past 4 weeks. h) Subjects who have
received a live-virus vaccine within 30 days before study drug administration.
3. Physical and Laboratory Test Findings. 1. Any positive test for hepatitis B virus or hepatitis C virus indicating acute
or chronic infection.
2. Known history of testing positive for human immunodeficiency virus (HIV) or
known acquired immunodeficiency syndrome (AIDS).
3. ECG demonstrating a QTcF interval >470 msec or patients with congenital long QT
syndrome.
4. Allergies and Adverse Drug Reaction. 1. History of allergy to study drug components.
2. History of severe hypersensitivity reaction to any monoclonal antibody. 5. Sex and Reproduction Status. 1. WOCBP who are pregnant or breastfeeding.
2. Women with a positive serum or urine pregnancy test at enrollment or prior to
administration of study medication.
6. Other Exclusion Criteria. 1. Prisoners or subjects who are involuntarily incarcerated, or other vulnerable
populations (study is exempt from 45 CFR 46 Subparts B, C, and D).
2. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness.
