Enrollment Begins for Phase 2 Trial of IMNN-001 Plus Bevacizumab/Chemo in Advanced Ovarian Cancer

Amir Jazaeri, MD

Enrollment has commenced for a phase 2 trial (NCT05739981) investigating the DNA-based interleukin-12 (IL-12) immunotherapy IMNN-001 (formerly GEN-1) in combination with bevacizumab (Avastin) and chemotherapy in patients with advanced ovarian cancer.¹

The study is expected to enroll 50 patients with stage III/IV advanced ovarian cancer, and it is being led by principal investigator Amir Jazaeri, MD, the vice chair for Clinical Research and director of the Gynecologic Cancer Immunotherapy Program in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center.

“The medical need for new innovative therapeutic approaches in ovarian cancer is major. The majority of patients with ovarian cancer are diagnosed with stage III/IV disease and face low cure rates of 15% or less,” Corinne Le Goff, PharmD, MBA, president and chief executive officer of IMUNON, stated in a news release. “The amount of data this study will generate will be a huge contribution to the treatment of ovarian cancer, and we believe the combination of IMNN-001 and bevacizumab has important potential.

“In our animal studies, the combination clearly showed strong synergies. We are hoping that with this study we can potentially transform the current treatment landscape and provide new hope to women suffering from this deadly cancer.”

IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein.

Previously reported data from the phase 1 OVATION 1 trial (NCT02480374) showed that the combination of IMNN-001 plus chemotherapy demonstrated activity and safety in patients with advanced epithelial ovarian cancer. Among 14 enrolled patients, 12 (85.7%) experienced a radiological response, including 2 complete responses and 10 partial responses.²

The most common treatment-emergent adverse effects that were at least possibly related to treatment included nausea, fatigue, abdominal pain/cramping, anorexia, diarrhea, and vomiting. Grade 4 neutropenia occurred in 8 patients, and this was attributed to neoadjuvant chemotherapy. No dose-limiting toxicities were reported.

The phase 2 trial is enrolling patients with a suspected diagnosis of high grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with histologic confirmation per pre-treatment biopsies.³ Patients are also required to have an International Federation of Gynecology and Obstetrics stage of III or IV that has been determined to benefit from neoadjuvant therapy.

Other key inclusion criteria include the discontinuation of any hormonal therapy directed at the tumor within at least a week prior to first study treatment, an ECOG performance status of 0 or 1, and adequate bone marrow, renal, hepatic, and neurologic function.

The trial is excluding patients who have received prior treatment with IMNN-001; have had treatment with corticosteroids within 2 weeks of study entry or have a clinical requirement for ongoing systemic immunosuppressive therapy; have autoimmune disease requiring immunosuppressive therapy within the past 2 years; or have received prior radiotherapy or chemotherapy to any portion of the abdominal cavity or pelvis.

Enrolled patients are being randomly assigned 1:1 to receive chemotherapy plus bevacizumab with or without IMNN-001. Chemotherapy will consist of 175 mg/m2 of paclitaxel followed by area under the curve 5/6 of carboplatin on day 1 of each 21-day cycle. Neoadjuvant chemotherapy will consist of 4 to 6 cycles per investigator’s discretion, and adjuvant chemotherapy will last for another 3 cycles.

Bevacizumab will be administered at 15 mg/kg on day 1 of cycles 2, 3, 6, and 7, and bevacizumab will also be given as a single agent every 3 weeks during the maintenance phase for up to 18 cycles, or until disease progression or unacceptable toxicity. In total, bevacizumab will be given in up to 22 cycles.

Patients in the experimental arm will be given 80 mg/m2 of IMNN-001 once per week on day 15 of cycle 1 and continued through the end of adjuvant therapy. Following the conclusion of chemotherapy, IMNN-001 will be administered every 21 days with bevacizumab in patients who are BRCA negative and homologous recombination proficient.

The primary end point of the study is reducing the minimal residual disease–positivity rate at second look laparoscopy from an expected 70% in the control group to 35% in the experimental group. Secondary end points include progression-free survival and overall survival.

“Break Through Cancer is excited to support this important study,” Tyler Jacks, PhD, president of Break Through Cancer, founding director of MIT’s Koch Institute for Integrative Cancer Research, and the David H. Koch Professor of Biology, stated in a news release.¹ “Our foundation has brought together some of the nation’s top cancer research centers to collaborate, accelerate research and clinical trials, and ultimately intercept and find cures for the deadliest cancers.”

The phase 1/2 OVATION 2 trial (NCT03393884) is also evaluating IMNN-001 plus paclitaxel/carboplatin vs chemotherapy alone.⁴

References

1. IMUNON and Break Through Cancer commence enrollment in a phase 1/2 clinical study of IMNN-001 in combination with Avastin in advanced ovarian cancer. News release. IMUNON. February 27, 2023. Accessed February 28, 2023. https://investors.imunon.com/news-releases/
2. Thaker PH, Bradley WH, Leath CA, et al. GEN-1 in combination with neoadjuvant chemotherapy for patients with advanced epithelial ovarian cancer: a phase I dose-escalation study. Clin Cancer Res. 2021;27(20):5536-5545. doi:10.1158/1078-0432.CCR-21-0360
3. A phase II study evaluating the effect of GEN-1 on SLL when administered in combination with bevacizumab and NACT in subjects newly diagnosed with advanced ovarian, fallopian tube or primary peritoneal cancer (MRD). ClinicalTrials.gov. Updated February 22, 2023. Accessed February 28, 2023. https://clinicaltrials.gov/ct2/show/NCT05739981
4. Study of GEN-1 with NACT for treatment of ovarian cancer (OVATION 2). ClinicalTrials.gov. Updated February 28, 2023. Accessed February 28, 2023. https://clinicaltrials.gov/ct2/show/NCT03393884