Phase I/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors.

Purpose: We conducted a phase I/II study to evaluate durvalumab (D; anti-PD-L1) in combination with tremelimumab (T; anti-cytotoxic T-lymphocyte antigen 4) in pediatric patients with relapsed/refractory solid tumors. Patients and methods: The dose-finding phase (phase I) assessed the safety and pharmacokinetics of D+T at two dose levels to determine the recommended phase II dose (RP2D). The primary endpoint for the dose-expansion phase (phase II) was antitumor activity (by Response Evaluation Criteria in Solid Tumors v1.1) at the RP2D. Assessment of circulating cells reflecting immune cell activation was a secondary endpoint. Results: Based on safety and pharmacokinetic data in the dose-finding phase (n = 29), the adult-equivalent RP2D was determined as D (30 mg/kg) + T (1 mg/kg). In the dose-expansion phase, 21 patients (sarcoma, n = 11; solid tumors, n = 10) were treated at the RP2D. Of patients with sarcoma, none achieved an objective response and one had stable disease ≥7 weeks. Of the patients with solid tumors, one (chordoma) had a confirmed partial response (10.8 months duration) and one (renal cell carcinoma) had stable disease ≥7 weeks. Treatment-related adverse events occurred in 76% of patients (19% as grade 3 or 4). No adverse events leading to death were reported. Across both phases treatment with D+T resulted in an increase in CD4+Ki67+ T cells. Conclusions: D (30 mg/kg) + T (1 mg/kg) had limited antitumor activity in this pediatric population; however, the safety profile was manageable and consistent with the known safety profile in adult patients, with no new safety concerns identified. Clinical trial registration: ClinicalTrials.gov, identifier NCT03837899; EudraCT, identifier 2018-003118-42.