Oregovomab in combination with non-platinum chemotherapy for the treatment of PARP inhibitor– and platinum-resistant ovarian cancer: A two-cohort, single-arm phase 2 study (OPERA/KGOG3065/APGOT-OV6).

5587 Background: Oregovomab, an investigational murine monoclonal antibody against CA-125, has shown promising efficacy in a phase 2 study in patients with recurrent ovarian cancer. Herein, we report the primary results of OPERA/KGOG 3065/APGOT-OV6 on oregovomab in combination with non-platinum-based chemotherapy in patients with PARP inhibitor (PARPi)- and platinum-resistant epithelial ovarian cancer (EOC). Methods: This multicenter, investigator-initiated, two-cohort, single-arm phase 2 trial evaluated the efficacy and safety of oregovomab in combination with PLD or weekly paclitaxel in patients with PARPi- and platinum-resistant EOC. Patients who received one to three prior lines of chemotherapy will be assigned to Cohort 1 (oregovomab [C1,2,3,5,7 for five doses] + PLD q4w, n=28), whereas patients who received more than three prior lines of chemotherapy will be assigned to Cohort 2 (oregovomab [C1,2,3,5,7 for five doses] + weekly paclitaxel [D1,8,15 q4w], n=28). The primary endpoint of the study was objective response rate (ORR) based on RECIST version 1.1. The secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. For the exploratory endpoints, immunologic response was measured at pretreatment and at C2, 3, 5, 7, or EOT by assessing serum HAMA levels and performing flow cytometric analysis of PBMCs. This trial is registered with ClinicalTrials.gov (NCT05407584). Results: A total 56 patients (Cohort 1, n=28; Cohort 2, n=28) have been enrolled between July 12, 2022 and September 19, 2023. Median age was 59 years (range, 36–79). Fifty-two (92.9%) patients had high-grade serous adenocarcinoma. At the data cut-off, the median follow-up was 8.0 months for Cohort 1 and 6.5 months for Cohort 2. The ORR was 0.0% (95% CI: 0.0–12.3) in Cohort 1, and 28.6% (95% CI: 13.2–48.7) in Cohort 2. Eight patients (28.6%) in Cohort 2 achieved a partial response, while 12 (42.9%) patients in Cohort 1 and 3 (10.7%) patients in Cohort 2 had stable disease. Three patients withdrew from the study due to treatment-related adverse events (TRAEs). These included one case of neutropenia in Cohort 1 and cases of anemia and lymphedema in Cohort 2. No TRAEs leading to death were reported. The median PFS was 2.5 months (95% CI: 2.1–4.7) in Cohort 1, and 2.6 months (95% CI: 2.0–3.7) in Cohort 2. Serum HAMA levels significantly increased after C3 exclusively in Cohort 2, but no significant changes in peripheral T cells have been observed. Conclusions: Oregovomab plus weekly paclitaxel chemotherapy demonstrated encouraging activity and safety in heavily pre-treated PARPi- and platinum-resistant EOC. Clinical trial information: NCT05407584 .