Ceralasertib Plus Durvalumab in Chinese Patients with Advanced Solid Tumors: A Nonrandomized Clinical Trial

INTRODUCTION: This phase I, multicenter, nonrandomized open-label study is the first study to investigate the safety, pharmacokinetics, and antitumor activity of ceralasertib, an oral ATR kinase inhibitor, in combination with in Chinese patients with advanced solid tumors who are refractory or resistant to prior anti-PD-(L)1 immunotherapy or for whom no standard of care exists. METHODS: Patients were enrolled into one of two cohorts. Cohort 1 received ceralasertib 240 mg twice daily on days 1‒7 of cycle 0 then on days 22‒28 from cycle 1 onwards (28-day cycle). Cohort 2 received ceralasertib 160 mg twice daily on days 1‒14 of cycle 0 then on days 15‒28 from cycle 1 onwards (28-day cycle). All patients received durvalumab 1500 mg on day 1 (28-day cycle). Patients were treated until disease progression, discontinuation due to adverse events, or patient or investigator's decision to withdraw. The primary endpoint was safety and tolerability of ceralasertib combined with durvalumab. Secondary endpoints included ceralasertib pharmacokinetics and antitumor activity. RESULTS: Overall, 14 patients were enrolled (cohort 1, n = 8; cohort 2, n = 6). All patients were Chinese and the majority (85.7%) had received > 4 prior lines of therapy. Most patients (13/14; 92.9%) had an adverse event, which were grade ≥ 3 in 7 (50.0%) patients. No dose-limiting toxicities occurred (12 evaluable patients; six in each cohort). Pharmacokinetics for ceralasertib were comparable to that reported in other studies for monotherapy or in combination with durvalumab. Among 13 response-evaluable patients, 3/13 had a confirmed partial response (one with lung adenocarcinoma, one with squamous cell carcinoma of the cervix uteri, and one with lung squamous cell carcinoma); the objective response rate was 23.1% [80% CI 8.8‒44.4%]). CONCLUSIONS: Ceralasertib plus durvalumab had antitumor activity in Chinese patients with advanced solid tumors; safety and pharmacokinetics were consistent with studies in Western patient populations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05514132.