AN OPEN‐LABEL, PHASE 1/2 STUDY OF FRONTLINE BRENTUXIMAB VEDOTIN + ADRIAMYCIN, VINBLASTINE, AND DACARBAZINE IN PAEDIATRIC PATIENTS WITH ADVANCED STAGE HODGKIN LYMPHOMA

Introduction: Paediatric Hodgkin lymphoma (HL) has high cure rates, but in younger patients (pts) multiagent regimens are associated with serious sequelae from radiation and alkylating chemotherapy including: increased secondary malignancies, cardiovascular disease, hypothyroidism, infertility, pulmonary diseases, and infections. C25004 (NCT02979522) is a Phase (Ph) 1/2 open-label study to assess the safety and efficacy of frontline brentuximab vedotin + adriamycin, vinblastine, and dacarbazine (A+AVD) in paediatric pts with advanced-stage, classical HL (cHL). Methods: Eligible pts were aged 5 to <18 years, had untreated stage III/IV cHL, Lansky/Karnofsky Performance Status (LKPS) ≥50, and bidimensional measurable disease by radiography. In Ph1, pts received up to 6 28-day cycles of A+AVD on days 1 and 15 of each cycle, with brentuximab vedotin given as a 36 mg/m2 or 48 mg/m2 dose. Toxicity was evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events, v4.03. Ph 1 primary objectives were to assess safety and tolerability and to identify the recommended Ph2 dose (RP2D) of brentuximab vedotin. Ph2 primary objectives were to assess the objective response rate (ORR) (complete [CR] + partial remission [PR] rates), and to determine the proportion of pts achieving PET-negativity (Deauville score 1–3) after 2 cycles (PET2-), and the proportion of pts completing 6 cycles of therapy at the RP2D. The percentage of pts receiving radiotherapy (RT) after study treatment and the safety and tolerability of A+AVD were included as Ph2 secondary endpoints. Results: In total, 59 pts were enrolled (Ph1 n = 8, Ph2 n = 51), median age was 14 years (range 6–17), 53% were male and median LKPS was 90.0 (range 70–100). RP2D was 48 mg/m2 as reported by Franklin et al. (ASH 2018, abstract 1644); all pts received 6 cycles of A+AVD. Ph 1/2 results for the total population (N = 59) are reported hereafter. ORR per independent review facility at end of treatment was 88% (95% CI: 77, 95), 76% of pts (95% CI: 63, 86) achieved a CR. PET2- rate was 90% (95% CI: 79, 96). After 17.31 months (median) follow-up 13 pts (22%) had progressive disease. Safety data are summarised in the Table. The most common any-grade treatment-emergent adverse events (TEAEs) were vomiting (85%) nausea (75%), and neutropenia (58%); 41% of pts experienced serious AEs (SAEs). There were no on-study deaths. The research was funded by: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Keywords: Hodgkin lymphoma, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract F. A. V. Luisi Employment or leadership position: GRAACC Honoraria: GRAACC M. A. Pianovski Research funding: Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited M. A. Salvino Consultant or advisory role: Takeda Advisory Board Research funding: Brentuximab Clinical Trials HSR PI R. E. Norris Employment or leadership position: Merck Pharmaceuticals Educational grants: Merck Pharmaceuticals M. Zecca Consultant or advisory role: AMGEN, Bluebird, MEDAC Educational grants: JAZZ Pharmaceuticals Y. Sidi Employment or leadership position: Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited F. Campana Employment or leadership position: Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited E. J. Leonard Employment or leadership position: Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Stock ownership: Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited