Updated safety and efficacy data from an open-label, phase 1/2 study of frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) in pediatric patients with advanced-stage classical Hodgkin lymphoma (cHL).

10000 Background: A+AVD is approved for treatment of adult patients with previously untreated Stage III or IV cHL. Here we present updated results from a phase 1/2 open-label study of frontline A+AVD in treatment-naïve pediatric patients with advanced stage cHL. Methods: Patients aged 5 to < 18 years with CD30+, stage III or IV, newly diagnosed cHL received A+AVD on days 1 and 15 of each 28-day cycle for up to 6 cycles. In phase 1, eight patients were treated with 48 mg/m2 of brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (AVD). Dose-limiting toxicity (DLT) was evaluated from day 1 of cycle 1 to day 56. In phase 2, a further 51 patients were treated with the same regimen. Results presented here refer to phases 1 and 2 combined. Progression-free survival (PFS) was defined as the time from first dose to disease progression; event-free survival (EFS) was defined as the time from first dose to treatment failure, events included disease progression, treatment withdrawal or death. Data cutoff was September 24 2021, when all patients had been on study for at least 2 years. Results: In phase 1, no DLT occurred in the 6 DLT-evaluable patients. The maximum tolerated dose of brentuximab vedotin was not reached and 48 mg/m2 was determined to be the recommended dose. All 59 patients in phase 1 and 2 completed 6 cycles of A+AVD and all experienced ≥1 treatment-emergent adverse event (TEAE). The most common any-grade TEAEs were vomiting (85%), nausea (75%), and neutropenia (58%). In total, 14/59 patients (24%) developed treatment-emergent peripheral neuropathy (PN); 10 patients had PN resolved by end of treatment (EOT); by last contact, 13 patients had resolved PN and one patient had grade 1 paraesthesia. No patients died on study. The PET-negative rate (Deauville 1, 2, or 3) after cycle 2 was 90%. Objective response rate ([ORR], defined as complete response [CR] + partial response [PR] per independent review facility [IRF] at EOT) was 88%, and 76% of patients achieved a CR. Median duration of response and duration of CR were not estimable. Median PFS and EFS had not been reached, suggesting encouraging efficacy of the combination in this pediatric patient population. Additional PFS, EFS and overall survival data will be presented during the meeting. Conclusions: Brentuximab vedotin given at 48 mg/m2 every two weeks in combination with AVD had an acceptable safety profile and was associated with an efficacy benefit in CD30+, treatment-naïve pediatric patients with advanced cHL, supporting A+AVD as a frontline treatment option for this patient population. Clinical trial information: NCT02979522.