726P - Efficacy and safety of pembrolizumab plus olaparib combination therapy in recurrent cervical cancer progressed on platinum-based chemotherapy: Results from the phase II trial of GOTIC-025

Background

Patients with recurrent cervical cancer, especially those resistant to platinum-based chemotherapy, have limited treatment options. PD-1 blockade monotherapy stands out as one of the optimal choices in this context. PARP inhibition may exert an immune modulatory effect through the cGAS/STING pathway, and this phase II trial aims to explore the efficacy and safety of pembrolizumab (Pem) plus olaparib (Ola) in this patient cohort.

Methods

This multicenter investigator-initiated single-arm Phase II trial assesses the antitumor effects and survival outcomes of combining PD-1 inhibition with Pem and PARP inhibition with Ola. Eligible patients, who had prior platinum-based chemotherapies and no prior immunotherapy, received Pem (200mg every 3 weeks) and Ola (600mg per day) combination therapy until disease progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR) by RECISTv1.1.

Results

Between June 2021 and July 2022, twenty-eight patients were enrolled. Patient characteristics included a median age of 55 years, with 14 (50%) patients having squamous cell carcinoma and 14 (50%) adenocarcinoma/adenosquamous carcinoma. Twenty-two (79%) patients had more than 2 lines of chemotherapy, and 22 (79%) patients had a history of bevacizumab. Twenty-six of 28 patients were evaluable for antitumor activity, as two patients did not have RECIST evaluation after treatment initiation. The ORR was 7.7% and the disease control rate was 53.8%. The median PFS and OS were 3.4 and 11.9 months, respectively. No patients required Pem discontinuation, but 4 (14%) patients required Ola discontinuation due to adverse events (AEs). All patients and 21 (75%) patients experienced any grade of AEs due to Ola or Pem, respectively. Grade≥3 AEs were observed in 17 (61%) patients, with anemia (29%) and decreased white blood cell counts (11%) being the most common.

Conclusions

This trial investigates Pem plus Ola combination therapy in platinum-experienced recurrent cervical cancer, revealing manageable safety. However, limited activity was observed with the addition of Ola to PD-1 inhibition in this study.

Clinical trial identification

NCT04641728. First posted November 24, 2020.

Editorial acknowledgement

Legal entity responsible for the study

Gynecologic Oncology Trial and Investigation Consortium (GOTIC).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.