Vaccine Therapy in Stage II, III, or IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

This was a Phase 1, non-randomized, open-label, multicenter study of the ALVAC(2)-NY-ESO-1(M)/TRICOM vaccine administered with the granulocyte macrophage-colony stimulating factor (GM-CSF) sargramostim in patients with NY-ESO-1- or LAGE-1-positive epithelial ovarian, fallopian tube, or primary peritoneal cavity cancers who had completed standard therapy for primary or recurrent disease and would have normally entered a period of observation. The primary study objective was to determine the safety and tolerability of study vaccination, with secondary objectives including the determination of clinical and immunological responses.

Patients received subcutaneous (SC) injections with 0.5 mL of ALVAC(2)-NY-ESO-1(M)/TRICOM on Day 1 and 100 μg of the GM-CSF sargramostim on Days 1 through 4 in continuous 28-day cycles for up to 6 cycles. No dose escalation of either vaccine component was permitted. Patients received study vaccinations until disease progression or unacceptable toxicity.

Safety was evaluated by continuous monitoring of adverse events (AEs), concomitant medications, and vital signs, as well as through hematology and chemistry laboratory testing and physical examinations. Efficacy was determined through tumor response evaluations, cancer antigen (CA)-125 levels, and cellular and humoral immune responses (i.e., NY-ESO-1-specific T cells, antibodies to NY-ESO-1 and ALVAC, and delayed-type hypersensitivity \[DTH\] testing).

Eligibility Criteria:
Inclusion Criteria:

1. Histologically documented epithelial carcinoma arising in the ovary, fallopian tube or peritoneum, from stage II-IV at diagnosis, treated with initial surgery and chemotherapy with at least one platinum-based chemotherapy regimen.
2. Complete response to frontline therapy as evidenced by negative clinical examination, CA-125 tumor marker, and computed tomography (CT) scan. In addition, if second look surgery was performed (by laparoscopy or laparotomy), the result must have been either negative or microscopic positive. These patients would have normally entered a period of observation after standard management.
3. Patients with recurrent disease were eligible if they had completed surgery and/or chemotherapy for recurrent disease and would have normally entered a period of observation after completion of standard management. Eligible patients could have had asymptomatic residual measurable disease on physical examination and/or CT scan, and/or could have had an elevated CA-125 or could have been in complete clinical remission (defined as a serum CA-125 ≤ 35 IU/mL, CT scan without objective evidence of disease, and normal physical examination).
4. Tumor expression of 1) NY-ESO-1 by reverse transcription-polymerase chain reaction (RT-PCR) (preferably) or immunohistochemistry (IHC); or 2) LAGE-1 by RT-PCR. Patients whose primary surgery was performed outside the study site were pre-screened and required to release tissue sections or blocks to the study site in order to determine tumor expression of NY-ESO-1 by IHC.
5. Expected survival of at least 6 months.
6. Full recovery from surgery.
7. Karnofsky performance status of 70 or more.
8. Laboratory parameters for vital functions were required to be in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were required to be within the ranges specified:

   * neutrophil count: ≥ 1.5 × 10\^9/L
   * lymphocyte count: ≥ 0.5 × 10\^9/L
   * platelet count: ≥ 100 × 10\^9/L
   * serum creatinine: ≤ 2 mg/dL
   * serum bilirubin (total): ≤ 2 mg/dL
   * hemoglobin: ≥ 10 g/dL
9. Have been informed of other treatment options.
10. Age ≥ 18 years.
11. Able and willing to give valid written informed consent.

Exclusion criteria:

1. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
2. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
3. History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo.
4. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
5. Known immunodeficiency or human immunodeficiency virus positivity.
6. Known allergy or history of life-threatening reaction to GM-CSF.
7. Known allergies to eggs, neomycin, and bovine products, determined by history.
8. History of severe allergic reactions to vaccines or unknown allergens.
9. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.
10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.
11. Mental impairment that could have compromised the ability to give informed consent and comply with the requirements of the study.
12. Lack of availability for immunological and clinical follow-up assessment.
13. Previous NY-ESO-1 vaccine therapy.