Study of Supplemental Arginine With Chemotherapy and Immunotherapy in Platinum Resistant Ovarian, Fallopian Tube, and Peritoneal Cancer

Inclusion Criteria:

1. Must be at least 18 years of age
2. ECOG performance status of 0 or 1 (see Appendix A).

3. Patient must be a candidate for either cohort A or cohort B treatment backbone.

   • For patients enrolling on treatment cohort A, PD-L1 positivity must be ≥1. Patient's with PD-L1 positivity ≥1% can enroll in cohort B at physician's discretion.
   • If PD-L1 positivity is unavailable or is <1%, patients can only enroll on treatment cohort B.
4. Patients must have high-grade serous or endometrioid histology
5. Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to the prior therapy, unless after discussion with the medical monitor the AE(s) are deemed clinically non-significant and/or stable on supportive therapy
6. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

7. Patients must have adequate hematologic, liver and kidney functions prior to lead-in chemotherapy defined as:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L (1,500/μL)
   2. Platelet count ≥ 100 x 109 /L (100,000/μL) without platelet transfusion in the prior 10 days
   3. Hemoglobin ≥ 9.0 g/dL
   4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
   5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
   6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
   7. Serum albumin ≥ 2 g/dL.

Exclusion Criteria:

1. History of allergic reactions contributed to compounds of similar chemical or biological composition to R-Gene 10 or Arginaid.
2. Patient unwilling/unable to receive daily arginine treatment (IV or oral)
3. Patients with a history of serologically confirmed HSV-1 or HSV-2 outbreaks
4. Receiving systemic corticosteroids or have severe comorbities where treatment with corticosteroids may be required.
5. Actively treated auto-immune disease.
6. Taking medications that interfere with the urea cycle such as valproate or xanthine oxidase inhibitors.
7. Current intercurrent illnesses including active infection, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmias.
8. Patients with history of Peptic Ulcer Disease
9. Contraindications to receive standard of care treatment backbone with either paclitaxel, bevacizumab, pembrolizumab, or cyclophosphamide.