CALLA: Efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical cancer: A phase III, randomized, double-blind, multicenter study.

Abstract

TPS5597 Background: CCRT is the standard of care for locally advanced cervical cancer. CCRT with PD-1/PD-L1 pathway blockade may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. This Phase 3, randomized, multicenter, international, double-blind, placebo-controlled study is designed to determine the efficacy and safety of durvalumab with and following CCRT vs. CCRT alone in women with locally advanced cervical cancer (NCT03830866). Methods: The study will enroll immunotherapy-naïve adult patients (pts) with histologically confirmed cervical adenocarcinoma or cervical squamous or adenosquamous carcinoma (FIGO Stages IB2-IIB with node [N] positive and IIIA-IVA with any N) and no prior definitive surgical, radiation, or systemic therapy for cervical cancer. Approximately 714 pts will be randomized 1:1 to receive either durvalumab (1500 mg intravenously [IV]) or placebo every 4 weeks for 96 weeks. All pts will receive CCRT to the pelvis or pelvis + para-aortic radiotherapy field (45 Gy), followed by image-guided brachytherapy with cisplatin (40 mg/m2) IV or carboplatin (AUC2) IV once weekly for 5 weeks (6th dose optional). Randomization will be stratified by disease stage (FIGO Stage < III and N positive, FIGO Stage ≥III and N negative, or FIGO Stage ≥III and N positive) and region (US, Canada, EU, South Korea, and Japan vs. rest of the world). The primary endpoint is progression-free survival (assessed by investigator per RECIST v1.1 or histopathologic confirmation of local tumor progression). Secondary endpoints are overall survival, objective response and complete response (CR) rates, duration of response in pts with CR, incidence of local or distant disease progression or secondary malignancy, disease-related symptoms, and health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-CX24). Pharmacokinetics, immunogenicity, and safety of durvalumab will also be assessed. Pt enrollment is ongoing. Clinical trial information: NCT03830866.