A Trial to Evaluate Safety, Tolerability, and Preliminary Efficacy of Misetionamide (GP-2250) as Monotherapy or in Combination With Gemcitabine

Part 2 of the trial will use a 3+3 dose escalation design. Subjects will continue to receive treatment until disease progression assessed by RECIST V1.1 criteria, clinical disease progression as assessed by the Investigator, unacceptable toxicity, subject request for withdrawal or lost to follow-up, Investigator assessment that risk outweighs benefit or study closure by the Sponsor. Part 2 will study PROC patients with disease progression within 6 months of the last dose of platinum-based chemotherapy and maximum of 2 prior regimens with at least one regimen causing the patient to meet the definition of platinum resistance.

Abridged Inclusion Criteria:

• Capable of giving signed informed consent: Regulatory, Ethical, and Trial Oversight Considerations which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Subjects age > 18 years at the time of trial entry.
• Pathologically proven platinum-resistant epithelial ovarian, fallopian, or primary peritoneal cancer, with high-grade serous ovarian carcinoma (HGSOC) or a predominantly serous/endometroid component. Platinum-resistant disease, defined as disease progression within 6 months of last dose of platinum-based chemotherapy.
• Maximum of 2 prior regimens for platinum-resistant disease. Subjects who are positive for high FR alpha (defined per the FDA approved companion diagnostic test (ELAHERE prescribing information) must have received MIRV. Candidates for MIRV with contraindications or documented intolerance are eligible pending documentation of discussion with the Medical Monitor.
• CT/MRI evidence of measurable disease per RECIST Version 1.1 defined as at least one lesion not previously irradiated that can be measured at baseline as 10 mm in the longest diameter (except lymph nodes which must have a short axis of 15 mm). Tumor lesions in previously irradiated area or in area subject to other loco-regional therapy are usually not considered measurable unless progression has been demonstrated in the lesion. Lesions selected as targets for response assessment should not be biopsied.
• ECOG performance status of 0-1
• Subjects with known central nervous system metastasis must have undergone brain targeted treatment and must be asymptomatic or radiographically and clinically stable (including not requiring steroids or anti-seizure medications) for at least 4 weeks prior to enrollment.
• Subjects must have adequate organ function as indicated by the following laboratory values:

• Absolute neutrophil count (ANC) ≥ 1,500 /mL
• Platelets ≥ 100,000 / mL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
• Serum total bilirubin ≤ 1.5 × ULN
• Aspartate aminotransferase (AST), (Serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT), and (Serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastasis
• International Normalized Ratio (INR) and/or Prothrombin Time (PT) ≤ 1.5 × ULN
• Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN
• Serum Albumin ≥ 3 g/dL measured at two time points: no less than 2 weeks before the 1st dose of misetionamide and within one week prior to the 1st dose. Subjects showing a decrease of > 20% at the 2nd measurement are excluded.
• Limited concomitant radiotherapy for pain control is allowed in the 5 weeks prior to initial dose.
• Women of childbearing potential (WOCBP) must have a negative urine pregnancy test.
• Subjects must use adequate contraception for the duration of the trial and for at least 3 months after the last dose and refrain from tissue donation during this period. .
• All acute toxic effects of any prior anti-tumor therapy resolved to Grade < 1or baseline before start of dosing (exceptions are alopecia and Grade 2 peripheral neuropathy).

Abridged Exclusion Criteria:

• Diagnosis of any active malignancy other than platinum-resistant ovarian cancer within the past 2 years (not including non-melanoma skin carcinoma, ductal carcinoma in situ of the breast, or carcinoma in situ of uterine cervix treated with curative intent).
• Subjects has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonia or multiple allergies, clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within < 6 months prior to the start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or ascites requiring paracentesis in the 4 weeks prior to Screening.
• Primary refractory disease (defined as failure to achieve at least a partial response (PR) to their initial platinum-based chemotherapy).
• Radiotherapy (RT) to target lesions, chemotherapy, or other systemic anti-cancer therapy, including prior anti-angiogenic treatment (e.g. bevacizumab) within 4 weeks prior to starting treatment.
• Ascites including history of therapeutic paracentesis within the 2 weeks prior to signing informed consent.
• Any other medical, psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate and participate in the trial, or which would interfere with the interpretation of the results.
• Subject has undergone major surgery, other than diagnostic surgery within 4 weeks prior to Day 1 of treatment in this study.
• Prior history or current signs of hyphema or glaucoma.
• History of sickle cell disease or hereditary non-spherocytic hemolytic anemia.
• Baseline QTc interval >480 msec for female subjects or >450 msec for male subjects.
• Subject is unwilling or unable to comply with study procedures or planning to take a vacation for >7 consecutive days during the course of the study.
• First degree relative of the investigator, study staff or the sponsor.
• Any chemotherapy administered within 3 weeks or 5 half-lives (whichever is shorter) before first dose of misetionamide; other anti-cancer therapy (including surgery, radiotherapy, immunotherapy, hormone therapy, or targeted therapy) administered within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of misetionamide; or within 6 weeks in the case of certain therapies (mitomycin C and nitrosoureas).
• Investigational therapy administered within 4 weeks or 5-half lives (whichever is shorter) before the first dose of misetionamide.