Trial in progress: Phase II study of stereotactic body radiation therapy and atezolizumab in the management of recurrent, persistent, or metastatic cervical cancer.

Abstract

TPS5596 Background: There is no consistent recommendation for management of metastatic cervical cancer beyond first line therapy with chemotherapy and bevacizumab. Pembrolizumab is now approved for PD-L1 positive or MSI-H/dMMR metastatic or recurrent cervical cancer. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with atezolizumab with hypofractionated radiation therapy will improve objective response rate (ORR) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer. Methods: The study is designed as a prospective, single arm, nonrandomized, open-label, phase II trial of stereotactic body radiation therapy (SBRT) with 24 Gy in 3 fractions to patients with ≥ 2 metastatic sites followed 1 week later by atezolizumab (1200 mg IV every 3 weeks) for patients with recurrent, persistent, or metastatic cervical cancer. Dose reductions will not be allowed. The primary objective of the study is to evaluate the ORR by Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) criteria following SBRT and atezolizumab. Secondary endpoints include progression free survival, overall survival, local control, and adverse events. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit. A total of 26 patients will be enrolled. An interim analysis will be performed to assess efficacy after 13 patients become evaluable.This study is open with 2 patients enrolled at the time of submission. Clinical trial information: NCT03614949.