Pembrolizumab plus chemotherapy in frontline treatment of advanced ovarian cancer: Clinical and translational results from a phase 2 trial

Jeffrey A. How, Minghao Dang, Sanghoon Lee, Bryan Fellman, Shannon N. Westin, Anil K. Sood, Nicole D. Fleming, Aaron Shafer, Ying Yuan, Jinsong Liu, Li Zhao, Joseph Celestino, Richard Hajek, Margaret B. Morgan, Edwin R. Parra, Caddie D. Laberiano Fernandez, Claudio A. Arrechedera, Luisa Maren Solis Soto, Kathleen M. Schmeler, Alpa NickKaren H. Lu, Robert Coleman, Linghua Wang, Amir A. Jazaeri

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood. Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples. Findings: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39–23.00) and 57.43 months (95% CI 30.88–not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling. Conclusions: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker. Funding: This investigator-initiated trial was funded by Merck.

Original languageEnglish (US)
Article number100494
JournalMed
Volume6
Issue number1
DOIs
StatePublished - Jan 10 2025

Keywords

  • Translation to patients
  • clinical trial
  • combination chemotherapy
  • feasibility
  • immunotherapy
  • ovarian cancer
  • pembrolizumab
  • translational
  • tumor immune microenvironment

ASJC Scopus subject areas

  • General Medicine

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