Randomized Phase 2 Trial of Tremelimumab and Durvalumab in Combination Versus Sequentially in Recurrent Platinum-Resistant Ovarian Cancer

Authors

Emily M Hinchcliff
Anne Knisely
Naomi Adjei
Bryan Fellman
Ying Yuan
Ami Patel
Cai Xu
Shannon N Westin
Anil K Sood
Pamela T Soliman
Aaron Shafer
Nicole D Fleming
David M Gershenson
Raghunandan Vikram
Tharakeswara Bathala
David Vining
Dhakshina M Ganeshan
Karen H Lu
Charlotte C Sun
Larissa A Meyer
Amir A Jazaeri

Publication Date

4-1-2024

Journal

Cancer

Abstract

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS).

RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms.

CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described.

Keywords

ovarian neoplasms, immune checkpoint inhibitors, randomized controlled trial, patient reported outcome measures, immunotherapy

Comments

Trial registration: ClinicalTrials.gov NCT03026062.

Supplementary Materials

PMID: 38009662