Phase III study of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A plus AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as front-line treatment for advanced classical Hodgkin lymphoma (HL)

Anas Younes, John Radford, Stephen Maxted Ansell, Andrea Gallamini, Won Seog Kim, Tatyana A. Feldman, Mehdi Hamadani, Jeanenne Chung, Jingyuan Wang, Dirk Huebner, Joseph M. Connors

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    Background: Brentuximab vedotin, a CD30-targeted antibody-drug conjugate, has conditional approval in Europe for relapsed/refractory (RR) CD30-positive HL following autologous stem cell transplant (ASCT) or following ≥2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ABVD, a common front-line regimen for advanced HL, achieves complete response (CR) rates of 70–80%. However, 10–20% of patients (pts) are refractory to front-line treatment and up to 35% relapse after front-line multi-modality therapy. In pts with relapsed HL post-ASCT, single-agent brentuximab vedotin yields an objective response rate of 75% (CR, 33%; Chen ASH 2012). In a phase 1 study in treatment-naïve HL pts, A+AVD was associated with manageable toxicity and a CR rate of 96%; brentuximab vedotin + ABVD was contraindicated due to pulmonary toxicity (Ansell ASH 2012). We hypothesized that substituting bleomycin with brentuximab vedotin would eliminate bleomycin-associated pulmonary toxicity and improve progression-free survival (PFS) compared to a standard ABVD regimen. Methods: This ongoing, open-label, randomized, multicenter study (NCT01712490) will compare A+AVD vs ABVD in 1040 pts with stage III/IV classical HL. Primary endpoint: modified (m) PFS (death, progression, and receipt of chemotherapy or radiotherapy by pts not in CR after completing A+AVD or ABVD will count as progression event). Key secondary endpoint: overall survival. Key inclusion criteria: histologically-confirmed previously untreated stage III/IV classical HL. Pts will be stratified by region and International Prognostic Score, and will be randomized 1:1 to receive A+AVD (brentuximab vedotin 1.2 mg/kg with each dose of AVD) or ABVD administered intravenously on Days 1 and 15 of 28-day cycles, for up to 6 cycles. Disease status and survival will be evaluated regularly until study closure. Safety assessments: incidence and severity of adverse events, changes to physical and laboratory tests. Clinical trial information: NCT01712490.
    Original languageUndefined
    Article numberTPS8612
    JournalJournal of Clinical Oncology
    Issue number15 Suppl
    Publication statusPublished - 2013

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