Open-label, Phase I study of NeoVax with Nivolumab in Patients with Ovarian Cancer

Protocol # :
Ovarian Cancer
Disease Sites
Principal Investigator
Konstantinopoulos, Panagiotis, A.
Site Investigator
Harden, Maegan, V.
Ott, Patrick
Site Research Nurses
Arvine, Lisa, Beth
Baylies, Rosemarie
Bowler, Becky, L.
Cummings, Kelly
Earley, Catherine, B.
Flynn, Laura, Kelly
Gillen Mckay, Christine, A.
Hamel, Alison
Hindenach, Sarah
Hurley-Whalen, Christin
Hurley-Whalen, Christin
Keis, Rylee
Kelley, Kristina
Menon, Susanne
Morrissey, Stephanie, C.
Rowan, Jennifer, M.
Stewart, Ann, M.
Thistle, Katrina, M.
Yager, Naomi, Isabelle

Trial Description

This research study is evaluating a new type of vaccine called "Personalized NeoAntigen
Cancer Vaccine" in combination with Nivolumab (Opdivo®) for ovarian cancer.

Eligibility Requirements

Inclusion Criteria:

- Diagnosis of epithelial ovarian cancer, primary peritoneal or fallopian tube cancer.
High grade serous, high grade endometrioid, clear cell and carcinosarcoma
(carcinosarcomas only with high grade serous epithelial component) histologies are
allowed. Low grade histologies and mucinous histology are not allowed.

- Participants must be classified into one of two cohorts:

- Cohort A: Patients with newly diagnosed stage IIIC or stage IV epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are planned to undergo neoadjuvant
chemotherapy. Patients must be candidates for platinum-based chemotherapy and
previously untreated. At the time of pre-screening consent, patients must have disease
that is amenable to biopsy and are agreeable and can safely undergo biopsy.

- Cohort B: Patients with recurrent (first recurrence only) epithelial ovarian, primary
peritoneal or fallopian tube cancer with platinum sensitive disease defined as disease
progression greater or equal than 6 months but not more than 18 months after
completion of their last dose of first line platinum chemotherapy. Prior hormonal
therapy is allowed but no other therapy for recurrence is allowed, including no
chemotherapy, no targeted therapy, and no antiangiogenic therapy. Maintenance therapy
after first line chemotherapy is allowed. At the time of pre-screening consent,
patients must have measurable disease by RECIST 1.1 and disease that is amenable to
biopsy and are agreeable and can safely undergo biopsy.

- Eastern Cooperative Group (ECOG) performance status ≤2 (please see Appendix A)

- Age ≥18 years

- Patients must have adequate organ and bone marrow function:

- Haemoglobin ≥ 8.0 g/dL

- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

- White blood cells (WBC) > 2x109/L

- Platelet count ≥ 100 x 109/L

- Total bilirubin ≤ 1.5 x institutional upper limit of normal

- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver
metastases are present in which case it must be ≤ 5x ULN

- Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

- Negative serum β-HCG or urine pregnancy test

- Ability to understand and the willingness to sign a written informed consent document.

- Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures

- Women of childbearing potential (WOCBP) must agree to follow instructions for
method(s) of contraception for the duration of study treatment with Nivolumab and 5
months after the last dose of study treatment {i.e., 30 days (duration of ovulatory
cycle) plus the time required for the investigational drug to undergo approximately
five half-lives}.

Patients of non-childbearing potential are defined as those fulfilling at least one of the
following criteria:

- Have undergone a documented hysterectomy and/or bilateral oophorectomy;

- Have medically confirmed ovarian failure; or

- Achieved postmenopausal status, defined as follows: cessation of regular menses for at
least 12 consecutive months with no alternative pathological or physiological cause;
status may be confirmed by having a serum follicle-stimulating hormone (FSH) level
confirming the post-menopausal state

Exclusion Criteria:

- Non-epithelial tumors or ovarian tumors with low malignant potential (i.e. borderline

- Mucinous or low grade histologies (i.e. low grade serous or low grade endometrioid)

- Cohort A and B patients who have signed prescreening consent form and then, in the
opinion of the investigator, have progressed after 3 or 4 cycles of platinum-based
chemotherapy, are ineligible for the treatment part of the study and no vaccine will
be manufactured

- Prior immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody
(including Ipilimumab), or any other antibody or drug specifically targeting T cell
co-stimulation or immune checkpoint pathways

- Major surgery (other than debulking surgery for ovarian, primary peritoneal or
fallopian tube cancer) for any reason within 4 weeks prior to initiation of
vaccination and/or incomplete recovery from surgery

- Known brain metastases or leptomeningeal metastases because of their poor prognosis
and because patients often develop progressive neurologic dysfunction that would
confound the evaluation of neurologic and other adverse events. A scan to confirm the
absence of brain metastases is not required.

- Active or history of autoimmune disease (known or suspected). Exceptions are permitted
for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
condition requiring only hormone replacement, psoriasis not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger.

- Have a condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone equivalents) or other immunosuppressive medications within 14 days
prior to the first dose of study drug (Nivolumab). Inhaled or topical steroids and
adrenal replacement doses (≤ 10 mg daily prednisone equivalents) are permitted in the
absence of active autoimmune disease.

- Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric
illness that could, in the investigator's opinion, interfere with participation in
this study.

- Known allergy to tetanus toxoid

- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection requiring treatment, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia.

- Have any underlying medical condition, psychiatric condition, or social situation
that, in the opinion of the investigator, would compromise study administration as per
protocol or compromise the assessment of AEs.

- Pregnant women are excluded from this study because Nivolumab, personalized neoantigen
peptides, and Poly-ICLC are agents with unknown risks to the developing fetus.

- Nursing women are excluded from this study because there is an unknown but potential
risk of adverse events in nursing infants secondary to treatment of the mother with
Nivolumab, personalized neoantigen peptides, and Poly-ICLC.

- Have a history of an invasive malignancy, except for the following circumstance:
individuals with a history of invasive malignancy are eligible if they have been
disease-free for at least 2 years or are deemed by the investigator to be at low risk
for recurrence of that malignancy; individuals with the following cancers are eligible
if diagnosed and treated carcinoma in situ of the breast, oral cavity or cervix,
localized prostate cancer, basal cell or squamous cell carcinoma of the skin.

- Participants who are receiving any other investigational agents