The Safety and Antitumor Activity of the Combination of Oregovomab and Hiltonol in Recurrent Advanced Ovarian Cancer

This is a Phase Ib evaluation of the combination of an antibody immunization vaccine strategy
using oregovomab and an investigational stage immune adjuvant (poly ICLC / Hiltonol), both of
which have previously been used in combination with other cancer treatments and demonstrated
to be bioactive in advanced cancer, but which have not previously been combined together. The
doses selected for each agent have been selected previously through human clinical study for
use in immunization protocols as a well-tolerated and bioactive immune stimulatory dose. For
immunization purposes a maximum tolerated dose is not a relevant pharmacologic objective.
Rather this is an exercise in efficiently assessing a preliminary immunization protocol as a
cost effective product development strategy assessing the ability of the combination to
safely augment the immune signals measurable with either agent alone, both of which have been
titrated to the current dose based on the principle of bell shaped dose response in
immunization in prior studies.

Subjects with stable disease for whom a 12 week break from cytotoxic therapy for their
persistent and progressive advanced ovarian cancer is appropriate, who have signed informed
consent and for whom baseline clinical information including laboratory, radiologic and
physical documentation of their status is completed, will receive 4 cycles of
oregovomab/Hiltonol immunization every three weeks (weeks 0, 3, 6, and 9). Blood will be
obtained for the measurement of CA125 specific T cell immunity at 12 weeks before initiating
continuing salvage therapy according to the best clinical judgment of the investigator. At
week 16 the subjects will receive a final immunization with oregovomab/Hiltonol and at week
17 an additional blood draw for analysis of T-cell immunity.

Inclusion Criteria:

1. Female subjects with CA125-associated, advanced ovarian cancer (FIGO Stage III/IV)
previously treated and now presenting with recurrent or persistent disease.

2. Must have a histological diagnosis of epithelial adenocarcinoma of ovarian, tubal or
peritoneal origin that is persistent or progressive following multiple rounds of prior
standard of care and experimental therapy.

3. Must have had an elevated serum CA125 level twice the upper limit of normal (per
reference lab normal range) measured within 4 weeks of enrollment.

4. Must have measurable disease by radiographic or physical criteria suitable for
evaluation according to RECIST v1.1 for documentation of disease response or
progression.

5. Must have a Functional Performance Status of less than or equal to 2 on the ECOG scale
(Appendix VII).

6. Must have reached legal age to consent.

7. Must have medical assessment consistent with prognosis for an expected survival of at
least 6 months and be clinically appropriate to receive a 12 week hiatus from any
cytotoxic treatment according to the best clinical judgement of the treating
investigator.

8. Must have voluntarily agreed to participate and have signed the informed consent, and
are willing to complete all study procedures.

Exclusion Criteria:

1. Compromised hematopoietic function (hemoglobin <8.0 g/dL; lymphocyte count <300 mm3;
neutrophil count <1000 mm3; platelet count <100,000 mm3).

2. Hepatic dysfunction defined as a bilirubin >1.5 times the upper normal limits, LDH,
SGOT and SGPT>2 times upper limits of normal or albumin <3.5 g/dL.

3. Renal dysfunction defined as a serum creatinine >1.6 mg/dL.

4. Pregnant or breast-feeding. (While pregnancy is unlikely in view of the disease and
previous surgery, subjects whom the investigator considers may be at risk of pregnancy
will have a pregnancy [beta-HCG] test and will be using a medically approved
contraceptive method).

5. Have an active autoimmune disease (e.g., rheumatoid arthritis, SLE, ulcerative
colitis, Crohn's Disease, MS, ankylosing spondylitis) requiring continuing immune
suppressive therapy.

6. Known allergy to murine proteins or have had a documented anaphylactic reaction to any
drug, or a known hypersensitivity to diphenhydramine or other antihistamines of
similar chemical structure.

7. Chronically treated with systemic doses of immunosuppressive drugs such as
cyclosporin, ACTH, or corticosteroids.

8. Active infection causing fever.

9. Recognized immunodeficiency condition including cellular immunodeficiencies,
hypogammaglobulinemia or dysgammaglobulinemia; subjects who have acquired, hereditary,
or congenital immunodeficiencies, including HIV infection or have been splenectomized.

10. Uncontrolled diseases other than cancer will be excluded. Subjects with chronic
diseases that are well controlled (e.g., diabetes mellitus, hypertension) are
eligible.

11. Have received other investigational drugs within 30 days of enrollment.

12. Have contraindications to the use of pressor agents (e.g., SC epinephrine), notably
monoamine oxidase inhibitor (MAOI) use.

13. Unable to read or understand, and/or unwilling to sign a written consent form which
must be obtained prior to treatment.

14. Known to have recent history of drug abuse or alcoholism.

15. Have participated in a prior oregovomab clinical trial. Prior treatment with Hiltonol®
does not exclude a subject from participation.