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

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

This is an open-label, Phase 1 clinical study to evaluate the safety, tolerability, PK profiles, and clinical activity of IV and PO arginine supplementation + SOC chemoimmunotherapy regimens in participants with PROC.

This is a Phase I, investigator-initiated and open-label study. Patients will be evaluated and treated at University of Alabama Birmingham Hospital. Patients will receive both oral and IV arginine with the physician choice of paclitaxel, pembrolizumab, +/- bevacizumab or pembrolizumab, bevacizumab, and oral cyclophosphamide, where doses and schedule are consistent with standard of care. Patients who are excluded from the trial due to progression will be scheduled for three- and six-months follow-up evaluations after the last dose. The goal for enrollment will be 6-24 patients with a 3-patient safety dose escalation lead-in using a 3+3 enrollment model for each regimen.

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.