760P - Cadonilimab with neoadjuvant chemotherapy in advanced ovarian cancer patients (AK104-IIT-003): An open, prospective, single arm, phase II trial

Background

There is an unmet need to improve neoadjuvant chemotherapy (NAC) to decrease postoperative residual disease and improve prognosis in ovarian cancer (OC). R0 rate and histopathological response of interval cytoreductive surgery (IDS) after NAC combined with immune checkpoint blockades were reported to be encouraging. Cadonilimab (AK104) is a tetravalent bispecific antibody targeting PD-1 and CTLA-4. In this study, we report the efficacy and safety of AK104 with NAC in patients with advanced-stage OC (NCT05430906).

Methods

This study is an open-label, prospective, single arm, phase II study of evaluating the efficacy and safety of cadonilimab combined with chemotherapy as neoadjuvant treatment for advanced OC. Patients received neoadjuvant therapy of AK104 plus NAC followed by surgery. Surgery would be performed within 30 days of completion of neoadjuvant therapy. The primary endpoint was the R0 rate. The secondary endpoints included objective response rate (ORR), chemotherapy response score (CRS), pathologic complete response(pCR), progression-free survival (PFS), and safety.

Results

24 patients were enrolled from Dec 12, 2022, to Apr 26, 2024. Most patients presented with high-grade serous carcinoma (95.8%) and FIGO stage IVa(16.7%), IVb disease (66.7%). 19 (79.2%) patients had undergone IDS with an R0 resection rate of 73.7%. ORR was 95.8%, including 4.2% CR. 14.3% achieved pCR, and 12.5% had a CRS of 3. PFS or OS data are not mature by cut-off date. Safety and adverse event (AE) were analyzed after completion of neoadjuvant therapy. Treatment-related AEs (TRAEs) of any grade were evaluated for all study populations. TRAEs of any grade occurred in 15 (62.5%) patients. Grade ≥3 TRAEs occurred in 3 (12.5%) patients. The most common TRAEs were thyroid dysfunction (19.0%), skin rash (12.5%) and bone marrow suppression (12.5%). Grade ≥ 3 irAE (immune-mediated colitis) occurred in 1 (4.2%) patient. All of the TRAEs, including severe AEs, were manageable, with no new safety concerns in this study.

Conclusions

This study showed promising activity, supporting the potential of NAC with cadonilimab in advanced-stage OC. Meanwhile, long-term efficacy evaluation still needs following up.

Clinical trial identification

NCT05430906. First Posted: 2022-06-24.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.