Background: CD30 is a cell surface antigen expressed on malignant HL Reed-Steenberg cells and targeted by the antibody-drug conjugate (ADC) brentuximab vedotin (ADCETRIS®), which comprises a CD30-targeted monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E via a protease-cleavable linker. Brentuximab vedotin has received US and European approval for treatment of RRHL following failure of autologous SCT (ASCT) or following ≥2 prior therapies when ASCT or multiagent chemotherapy is not a treatment option. Treatments are limited for patients ineligible for ASCT or multiagent chemotherapy; results of this ongoing Phase 4 trial (NCT01990534) will further investigate the anti-tumor activity of brentuximab vedotin in this difficult-to-treat population.
Methods: Eligible patients are ≥18 years of age with Eastern Cooperative Oncology Group performance status 0–1, RRHL after ≥1 prior therapy, and considered ineligible for SCT or multiagent chemotherapy due to progression within 90 days of complete response (CR) or unconfirmed CR to multiagent frontline chemo/radiotherapy, progressive disease (PD) during frontline multiagent chemotherapy, or relapse after ≥2 prior treatments (including salvage). Patients must have measurable disease (≥1.5 cm) by CT scan. Patients will receive an intravenous infusion of brentuximab vedotin 1.8 mg/kg on day 1 of 21-day cycles for up to 16 cycles or until disease progression or unacceptable toxicity. The primary objective is overall response rate (ORR) assessed by an independent review committee; secondary objectives include duration of response, CR rate, progression-free survival (PFS), overall survival (OS), pharmacokinetics, immunogenicity, safety and tolerability, and proportion of patients receiving ASCT or allogenic SCT following brentuximab vedotin treatment. CT scans of chest, neck, abdomen, and pelvis will be performed at baseline and cycles 2, 4, 7, 10, 13, and 16; PET scans at baseline and cycles 4 and 7. Post treatment follow-up for PFS and OS will be performed every 3 months, for 18 months after end of treatment. OS assessment will continue thereafter every 6 months until death or study closure. Incidence and severity of adverse events will be evaluated according to NCI CTCAE v.4.03. Enrollment has finished with 60 patients across 20 international sites. Final data will be provided at the congress.