Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma

N. Bartlett, A. Forero-Torres, J. Rosenblatt, et al

Methods: A multicenter phase I weekly dosing, dose-escalation study was conducted in 34 patients (mean age 34) with refractory or recurrent Hodgkin lymphoma or systemic anaplastic large-cell lymphoma. Patients had received a median of 5 prior therapies and 62% had undergone autologous stem cell transplantation. The study was conducted to determine whether more frequent dosing might maximize antitumor activity with acceptable tolerability. SGN-35 was administered weekly at doses of 0.4–1.4 mg/kg (2-hour IV infusions). After two 28-day cycles (6 doses), patients with stable disease or better were eligible to continue SGN-35 treatment, and 27 were evaluable.

Results: Complete responses were reported in 10 patients; partial responses in 3, with stable disease in 11 and progressive disease in 3. Some reduction in tumor was found in 81% of patients. Median duration of response is at least 16 weeks (0.1+ to 27.1+ wk). Grade 3 neutropenia was reported in 3 patients and diarrhea, paresthesia, vomiting and leukopenia were each reported once. Among grade 4 events, neutropenia and hyperglycemia were each reported once. No grade 5 events were reported. Overall, the most common drug-related adverse events were nausea (26%), fatigue (24%), peripheral neuropathy (18%), and neutropenia (18%). Dose-limiting toxicities were reported in 1 patient at 1.0 mg/kg and in 2 patients at 1.4 mg/kg.

Conclusions: SGN-35 was generally well tolerated. It demonstrated robust antitumor activity in heavily pretreated CD30+ malignancies. The overall response rate (CR+PR) was 48% (13/27). Phase II studies are currently enrolling patients.