Investigation of the Anti-tumor Effect of 2X-121 in Patients With Recurrent, Advanced Ovarian Cancer

Phase 2, Randomized, Prospective, Open-Label, Parallel-Arm, Dose Optimization Study to Investigate the Safety, Tolerability, PK/PD, and Anti- Tumor Effect of 2X-121 in Patients With Recurrent, Advanced Ovarian Cancer.

The purpose of this study is to evaluate the optimal dose of 2X-121 as single agent therapy at 600 mg daily (split BID 200 mg morning + 400 mg evening) compared to 800 mg daily (split BID 400 mg morning + 400 mg evening) in recurrent, advanced ovarian cancer patients that have platinum-resistant disease, defined as progression within 6 months after the last dose of platinum-based chemotherapy, or are platinum ineligible. The optimal dose will be selected based on an integrated analysis of PK/PD, safety, and efficacy data.

Inclusion Criteria:

1. Signed informed consent form.

2. Age 18 years or older.

3. Histologically or cytologically documented epithelial ovarian, fallopian tube, or primary peritoneal tumors, with high-grade serous or endometrioid, or predominantly serous/endometrioid histology (independent of BRCA1 and HRD status).

4. Patients must have platinum-resistant disease, defined as progression within 6 months after the last dose of platinum-based chemotherapy, or are platinum ineligible.

5. Patients have received no more than one line of therapy in the platinum resistant or platinum ineligible setting. Note: Prior ADCs therapy (e.g., Elahere) will not count towards this previous line of therapy.

6. Measurable disease by CT scan or MRI. Note: Baseline tumor assessment will be performed within 4 weeks prior to Day 1 Cycle 1

7. Performance status of ECOG ≤ 1.

8. Patients must have a life expectancy of >16 weeks.

9. Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy, or treatment with cytotoxic, hormonal, or biologic agents.

10. Adequate conditions as evidenced by the following clinical laboratory values:

    1. Absolute neutrophils count (ANC) ≥ 1.5 x 103 μL
    2. Hemoglobin > 9.0 g/dL
    3. Platelets ≥ 100 x 103 μL
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 x ULN, unless liver metastases are present, in which case they must be ≤5 x ULN
    5. Serum bilirubin ≤ 1.5 ULN
    6. Creatinine ≤ 1.5 ULN
    7. Blood urea nitrogen (BUN) ≤2X ULN.

11. FFPE tumor tissue should be available from the current relapse, if obtainable, otherwise the most recent archival tumor tissue. Note: Patients treated with a PARP inhibitor must have a new biopsy unless there is an archival biopsy that was done after the PARP inhibitor treatment was discontinued.

12. Negative serum pregnancy test in women of childbearing potential (WOCBP). WOCBP is defined as premenopausal women or less than 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization or hysterectomy or bilateral salpingo-oophorectomy.

13. Sexually active females of childbearing potential must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.

Exclusion Criteria:

1. Patients who have platinum-refractory disease, defined as progression during the last platinum-based chemotherapy.

2. Concurrent chemotherapy, antibody therapies radiotherapy,hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.

3. Other malignancy with exception of any stage I and II cancer that is deemed cured by the Investigator.

4. Any active infection requiring parenteral or oral antibiotic treatment.

5. Known HIV positivity.

6. Known active hepatitis B or C.

7. Clinically significant cardiovascular disease:

   1. Stroke within ≤ 12 months prior to day 1
   2. Transient ischemic attach (TIA) within ≤ 12 months prior to day 1
   3. Myocardial infarction within ≤ 12 months prior to day 1
   4. Unstable angina
   5. New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
   6. Uncontrolled cardiac arrhythmia requiring medication

8. Other medications or conditions that in the Investigator's opinion would contraindicate study participation for safety reasons or interfere with the interpretation of study results.

9. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of 2X-121.

10. Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.

11. Patients unable to be regularly followed for any reason (geographic, familiar, social, psychological, housed in an institution e.g., prison because of a court agreement or administrative order).

12. Patients, who are close colleagues, associates, or family members of, or in any way dependent on the sponsor or the investigator.

13. Ascites requiring drainage >500cc in the 2 weeks prior to enrolment.