SX-682 Treatment in Subjects With Metastatic Melanoma Concurrently Treated With Pembrolizumab

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Cancers attract myeloid-derived suppressor cells (MDSCs) that prevent our own immune responses from destroying the cancer. This study will be the first study to begin to determine if the newly discovered drug SX-682 can block cancers from attracting MDSCs. This first study will enroll participants with melanoma, as melanoma cancer has been shown to be able to attract MDSCs. The study will begin to determine if SX-682 is a safe and effective treatment of melanoma. It is thought that SX-682 will block MDSCs from going to the cancer, and thus will allow a patient's own immune system to attack the cancer.

The first participants enrolled in the study will receive for 21 days SX-682 as monotherapy. After 21 days participants will receive pembrolizumab therapy (an approved immunotherapy for melanoma) and will remain in the study for evaluations for 3 months.

After these participants complete the monotherapy stage, the next participants will receive SX-682 and pembrolizumab together as combination therapy. These participants will receive the combination therapy and be evaluated in the study for approximately 2 years.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Syntrix Biosystems, Inc.
• Collaborators: Dana-Farber Cancer Institute; Massachusetts General Hospital; Mayo Clinic; National Cancer Institute (NCI); The Wistar Institute; University of Rochester
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

• Subjects must have the nature of the study explained to them.

• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, pharmacokinetic collections, and other requirements of the study.

• Subjects must provide a signed and dated IRB/IEC approved written informed consent form (ICF) in accordance with regulatory and institutional guidelines.

• Subjects must provide a signed and dated Health Insurance Portability and Accountability Act (HIPAA) authorization.

• The ICF and HIPAA authorization must be obtained before conducting any procedures that do not form a part of the subject's normal care.

• 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:

• Histologically confirmed unresectable Stage III or Stage IV melanoma as per AJCC staging system.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

• 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 at least 3 weeks 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).

• Must have measurable disease with at least 1 unidimensional measurable lesion per RECIST v1.1.

• 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.

• Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.

• 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

• Glomerular filtration rate (GFR) calculated by Cockcroft-Gault formula >60 ml/min.

• No known positivity for human immunodeficiency virus (HIV) (no laboratory testing is required), no active infection with Hepatitis B or Hepatitis C.

• Life expectancy > 12 weeks.

• 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.

• Men and women, ages > 18 years of age.

• 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.

• 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.

• 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.

• Women must not be breastfeeding.

• 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.

• Women who are not of childbearing potential and azoospermic men do not require contraception.

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI - except where contraindicated, in which CT scan is acceptable) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. 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.

• Ocular melanoma (mucosal melanoma is acceptable).

• 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:

Subjects with active, non-infectious pneumonitis. Subjects with interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

Subjects with clinically significant heart disease that affects normal activities.

• 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.

• Subjects with active, known or suspected autoimmune disease (Appendix 3). 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.

• 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.

• Use of other investigational drugs (drugs not marketed for any indication) within 30 days before study drug administration.

• Subjects who have had major surgery in the past 4 weeks.

• Subjects who have received a live-virus vaccine within 30 days before study drug administration.

• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.

• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

• ECG demonstrating a QTc interval >470 msec or patients with congenital long QT syndrome.

• History of allergy to study drug components.

• History of severe hypersensitivity reaction to any monoclonal antibody

• Women of childbearing potential who are pregnant or breastfeeding.

• Women with a positive pregnancy test at enrollment or prior to administration of study medication.

• Prisoners or subjects who are involuntarily incarcerated, or other vulnerable populations (study is exempt from 45 CFR 46 Subparts B, C, and D).

• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness