Trial Information

Phase Ib Trial of Folate Binding Protein (FBP) Peptide (E39) Vaccine in Ovarian and Endometrial Cancer Patients

In this study, investigators intend to assess the safety and document local and systemic
toxicity to the folate binding protein (FBP) peptide vaccine E39 + GM-CSF given in the
adjuvant setting. Investigators also intend to determine the maximum tolerated dose (MTD)
and optimal biologic dose (OBD) for the peptide vaccine, as well as evaluate the in vivo
cellular immune response to the vaccine. Time to recurrence in the vaccinated patients vs.
matched controls will be tracked.

The primary endpoints are the safety and optimal dosing of the vaccine to induce an in vivo
peptide-specific immune response. The clinical endpoint is time to recurrence from date of
enrollment.

The study will be a multi-center, phase Ib trial of the FBP peptide E39 + GM-CSF. The
target study population is female civilian and military health care beneficiaries over the
age of 18 years with a diagnosis of FBP+ ovarian or endometrial cancer who have undergone
primary surgical and medical therapies, are post-menopausal or have surgically induced
menopause, and are currently without evidence of disease. Disease-free subjects after
standard of care multi-modality therapy will be screened and HLA typed since the E39 vaccine
is specific for HLA-A2+ patients (approximately 40% of the US population). HLA-A2-patients
will be followed as prospective clinically matched controls for recurrence.

HLA-A2+ patients who meet all other eligibility criteria will be tested for biomarkers that
indicate progression/recurrence of ovarian and advanced uterine cancer FBP. FBP+ and
HLA-A2+ patients will be vaccinated with the FBP peptide (E39) and GM-CSF. HLA-A2-negative
patients and those individuals who are eligible to receive the vaccine but who decline will
be followed clinically as matched controls for disease recurrence/progression.

Treatment will begin within 14 days of the subject enrollment in the study and confirmation
of eligibility. The 1 ml by volume vaccine will be administered intradermally in 0.5 mL
inoculums at two different sites within 5 cm of each other. A total of six vaccinations
will be given every 3-4 weeks and will be administered in the same lymph node draining area.
The dose escalation scheme is for three patients to receive each of the doses: 100, 500,
and 1,000 mcg of peptide. Patients will be enrolled consecutively. An additional three
patients may receive a given a dose depending on the presence of dose limiting toxicity
(DLT). Prior to the fourth vaccination, each patient will be assessed for liver, renal, and
hematopoietic function. If organ function is stable and no DLT is seen, then the patient
will continue with the series. After the last patient in a given dose group has completed
the third inoculation and organ function is proven stable, then the next dose group will be
initiated. Optimal biologic dose (OBD) is defined as the minimum dose of the vaccine that
gives the most optimal and lasting in vivo immunologic response to the vaccinated peptide.
Six patients will be vaccinated at the OBD.

Subjects will be followed for safety issues, immunologic response and clinical recurrence.
Subjects will be monitored 48-72 hours after each inoculation for reaction to the
inoculation as well as documentation of any adverse effects experienced. Immunologic
response will be documented with both ex vivo phenotypic and functional assays as well as in
vivo delayed type hypersensitivity (DTH) reactions. All patients will be followed for a
total of 36 months to document disease-free status.

The investigators intend to enroll up to 60 patients will be enrolled study-wide (15-24 in
the vaccine arm, up to 36 in the control arm). With accrual beginning in April 2012
enrollment of the last patient is anticipated to occur in April 2014 followed by a
three-year follow-up period. The duration of the trial is expected to be five years.