A Phase 1 / 2 Study Evaluating the Dosing, Safety, Efficacy, and Biological Activity of Intraperitoneal GEN-1 (IMNN-001) (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered in Combination With Neoadjuvant Chemotherapy (NACT) in Patients Newly Diagnosed with Advanced Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
While the standard of care for stage 3 and 4 ovarian cancer treatment can be successful, the current five-year survival rate still remains low, at less than 50%, with a relapse rate of 70%. There is a significant unmet need for more robust treatment options for ovarian cancer patients and their loved ones.
OVATION-2 is a randomized, open label, multicenter trial to evaluate the safety, dosing, efficacy, and biological activity of intraperitoneal GEN-1 (IMNN-001) immunotherapy plus NACT, compared to NACT alone in newly diagnosed patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Protocol Number: 201‑17‑201
Enrolling: Up to 130 subjects with newly diagnosed advanced ovarian cancer
Randomization: Randomly assigned 1:1 to receive either NACT plus GEN-1 (IMNN-001) or NACT alone
The Investigational Drug
Human IL-12 plasmid (phIL-12-005) is formulated with lipopolymer PEG-PEI-Cholesterol (PPC) in 10% lactose; classified as a biologic (nonviral gene therapeutic)
Infusion into abdominal cavity via an intraperitoneal catheter
Dose: 100 mg/m2
Study Design and Treatment Schedule:
paclitaxel 175 mg/m2 IV over 3 hours followed by carboplatin AUC 6 IV over 1 hour on Day 1; repeated every 3 weeks for 6 cycles [3 cycles chemo + surgery + 3 more cycles chemo]
100 mg/m2 IP will be administered on Days 8 and 15 of first NACT cycle and then on Days 1, 8, and 15 of the subsequent five 21-day NACT cycles for a total of 17 treatments (when given same day as NACT, GEN-1 (IMNN-001) should be given 30 minutes– to 3 hours after completion of NACT infusions)
Interval debulking surgery: will take place after 3 cycles of NACT
Key Inclusion Criteria
- A suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and confirmation per pretreatment biopsies by laparoscopy, or interventional radiology or CT / Ultrasound guided core biopsy. Histologic documentation of the original primary tumor is required via the pathology report.
- An International Federation of Gynecology and Obstetrics (FIGO) of III or IV.
- The following histologic epithelial cell types are eligible: High grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
- Hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to first treatment. Continuation of hormone replacement therapy is permitted.
- Performance status score of 0, 1, or 2 by Eastern Cooperative Group (ECOG) criteria.
Key Exclusion Criteria
- Subjects with other invasive malignancies are excluded if there is any evidence of the invasive malignancy being present within the last 3 years.
Prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded.
- Subjects who have received prior chemotherapy for any abdominal or pelvic tumor are excluded.
- Receiving treatment for active autoimmune disease.
- Oral or parenteral corticosteroids within 2 weeks of study entry or who have a clinical requirement for ongoing systemic immunosuppressive therapy such as chronic steroid use not related to chemotherapy administration.