IMNN-001 Plus Neoadjuvant Chemotherapy Improves PFS in Advanced Ovarian Cancer

Treatment with the interleukin-12 gene-mediated immunotherapy IMNN-001 (GEN-1) in combination with neoadjuvant platinum chemotherapy led to an improvement in progression-free survival (PFS) compared with neoadjuvant chemotherapy alone in newly diagnosed patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, according to interim data from the phase 1/2 OVATION 2 trial (NCT03393884).¹

Findings showed that treatment with the combination was associated with an approximate 33% delay in disease progression vs neoadjuvant chemotherapy alone. Data also demonstrated a trend toward an improvement in overall survival (OS), showing an approximate 9-month improvement with the addition of IMNN-001.

Notably, findings from a subgroup analysis also showed that patients treated with IMNN-001 plus neoadjuvant chemotherapy and a PARP inhibitor as maintenance therapy experienced an improvement in PFS and OS compared with those given neoadjuvant chemotherapy plus maintenance PARP inhibition alone.

Patients who received IMNN-001 plus chemotherapy and PARP inhibitor maintenance achieved a median PFS of 23.7 months compared with 15.7 months in those given chemotherapy and PARP inhibitor maintenance. The median OS was not yet reached for the IMNN-001 group compared with 45.6 months for the control group. Notably, this was not a prespecified subgroup since PARP inhibitors were not approved until after the start of OVATION 2.

Based on available data, IMUNON announced in a news release that the combination of neoadjuvant chemotherapy, IMNN-001, and PARP inhibition should be the focus moving forward since this regimen appears to provide the greatest benefit.

“We are encouraged by these interim results and are particularly intrigued by the OS trends in the subgroup of patients who received PARP inhibitors, neoadjuvant chemotherapy, and IMNN-001,” Corinne Le Goff, PharmD, president and chief executive officer of IMUNON, stated in a news release. “While the number of patients in this subgroup is relatively small, this regimen may hold potential in treatment strategies as we continue to monitor patients enrolled in OVATION 2, with expectations to report topline results in mid-2024.”

The open-label, randomized OVATION 2 study enrolled patients at least 18 years of age with suspected histologic diagnosis of International Federation of Gynecology and Obstetrics (FIGO) stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.2 They were required to have high-grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified. Other key inclusion criteria included an ECOG performance status of 0 to 2, and adequate bone marrow, renal, hepatic, and neurologic function.

Patients were excluded from the study if they received prior treatment with IMNN-001; received oral or parenteral corticosteroids within 2 weeks of enrollment or required ongoing systemic immunosuppressive therapy; had active autoimmune disease; received prior radiotherapy to any portion of the abdominal cavity or pelvis; or received prior chemotherapy for any abdominal or pelvic tumor.

The study enrolled 110 patients who were randomly assigned to receive neoadjuvant chemotherapy consisting of 175 mg/m² of intravenous (IV) paclitaxel and area under the curve 6 of IV carboplatin once every 3 weeks for 6 cycles, plus 100 mg/m² of IMNN-001 on days 8 and 15 of the first cycle of chemotherapy, then on days 1, 8, and 15 of subsequent cycles for a total of 17 doses; or the same neoadjuvant chemotherapy regimen alone.^1,2

PFS was the study’s primary end point. Secondary endpoints included OS, objective response rate, pathological response rate, surgical response, and serologic response.¹

Regarding safety, data demonstrated that IMNN-001 was well tolerated in this setting.

References

1. IMUNON reports interim progression-free survival and overall survival data in phase 1/2 OVATION 2 study in advanced ovarian cancer. News release. September 28, 2023. Accessed September 28, 2023. https://investors.imunon.com/news-releases/news-release-details/imunon-reports-interim-progression-free-survival-and-overall
2. Study of IMNN-001 (also known as GEN-1) with NACT for treatment of ovarian cancer (OVATION 2). ClinicalTrials.gov. Updated August 22, 2023. Accessed September 28, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03393884