GOG3035 Eligibility Criteria

Inclusion Criteria 

1. Adults 18 years old or older.

2. Subjects with newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.

3. Eligible histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).

4. Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator), as defined below:
a. For subjects who undergo primary debulking surgery (Cohort 1 - Primary Surgery):
i. Cycle 1 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after primary debulking surgery, and
ii. The primary debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).

b. For subjects who will undergo interval debulking surgery (Cohort 2 – NACT/Interval Surgery):
i. Subject must have received neoadjuvant treatment with 3 cycles of paclitaxel 175 mg/m2 IV over 3 hours every approximately 3 weeks (21 Days), followed by carboplatin area under the curve (AUC) 5-6 administered intravenously (IV) approximately every 3 weeks (21 Days), and
ii. Cycle 4 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after interval debulking surgery, and
iii. The interval debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).

5. Suitable venous access for the study-required procedures.

6. Cohort 1 – Primary Surgery: Preoperative serum CA-125 levels ≥ 50 U/mL, or in Cohort 2 – NACT + Interval Surgery: serum CA-125 levels ≥ 50 U/mL prior to first pre-operative chemotherapy.

7. Adequate bone marrow function:  a. Absolute neutrophil count (ANC) ≥ 1,500/μL
b. Platelets ≥ 100,000/μL                                                                                                                                                                         c. Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).             

8. Adequate liver function:
a. Bilirubin < 1.5 times upper limit normal (ULN)
b. Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
c. Albumin >3.5 g/dL

9. Adequate renal function:
a. Creatinine ≤ 1.5 times ULN

10. ECOG Performance Status of 0 or 1.

11. For women of childbearing potential, must be willing to avoid pregnancy by using a highly effective method of contraception from the first dose of study treatment to 60 days after last dose of study treatment. Adequate contraception is defined in Section 8.2.5.

12. Sign informed consent and authorization permitting release of personal health information.

13. Willingness and ability to complete patient quality of life questionnaires.

Exclusion Criteria 

1. BRCA1 or BRCA2 germline gene mutation test result with:
a. Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or
b. Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or
c. Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy.

2. Subjects with mucinous adenocarcinoma and low-grade adenocarcinoma.

3. Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment (C1D1 for Cohort 1 or C4D1 for Cohort 2).

4. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.

5. Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment.

6. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.

7. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G).

8. Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. (Note: Premedication with corticosteroids per institutional standard of care is allowed.)

9. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.

10. Clinically significant active infection(s) at the time of screening.

11. Any of the following conditions (on-study testing is not required):
a. Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or
b. Known or suspected hepatitis B if active infection (patients with chronic hepatitis B infection must have an undetectable HBV viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion), or
c. Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load).

12. Uncontrolled or life-threatening diseases compromising safety evaluation.

13. Diagnosed or treated for another malignancy within 5 years before the first dose, or previously diagnosed with another malignancy and have any evidence of residual disease. Subjects with non-melanoma skin cancer or cervix carcinoma in situ are not excluded if they have undergone complete resection. Synchronous endometrial cancer, but a prior diagnosis of endometrial cancer within 5 years is not excluded if all of the following conditions are met: Stage IA, superficial myometrial invasion, without lymphovascular invasion, grade 3 or not poorly differentiated subtypes including papillary serous, clear cell or other FIGO Grade 3 lesions.

14. Contraindications to the use of pressor agents.

15. Undergone more than one surgical debulking or have not recovered from surgery.

16. Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP-ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.

17. History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.

18. Any of the following cardiovascular conditions:
a. Acute myocardial infarction within 6 months before the first dose of study treatment.
b. Current history of New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H).
c. Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings.

19. Unable to read or understand or unable to sign the necessary written consent before starting treatment.