Durable complete remissions in a pivotal phase 2 study of SGN-35 (brentuximab vedotin) in patients with relapsed or refractory hodgkin lymphoma (HL)

Introduction: CD30 expression by Reed-Sternberg cells is a defining feature of HL. SGN-35 comprises an anti-CD30 antibody conjugated by a plasma-stable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). SGN-35 selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing MMAE. Methods: A pivotal, phase 2, single-arm, multicenter study evaluated the efficacy and safety of SGN-35 in patients (pts) with relapsed or refractory HL after autologous stem cell transplant (auto-SCT). Pts received SGN-35, 1.8 mg/kg q3 weeks (wks) as a 30?min. outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to Cheson 2007. Results: 102 pts were enrolled; 53% female, median age was 31 yrs (range 15 C77). Pts had received a median of 3.5 (range 1 C13) prior systemic therapies excluding auto- SCT.71% of pts had primary refractory disease and 42% had not responded to their most recent prior therapy. ORR per IRF was 75% (76 of 102 pts) with complete remissions (CRs) in 34% of pts (n=35). At the time of database lock (August 2010), median duration of follow up from first dose was ∼9 months (for responders). Median duration of response for pts with CR per IRF has not yet been reached (range 0.3+ to 61.4+ wks); follow up continues and 6+ months of additional data will be available for presentation. Treatment-related AEs of any grade in ≥ 15% pts were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea. AEs ≥ Grade 3 in ≥ 5% of pts were neutropenia, peripheral sensory neuropathy, thrombocytopenia, and anemia. Conclusions: With manageable AEs, single-agent SGN-35 induced objective responses in 75% of pts with relapsed or refractory HL. In this heavily pretreated population, 35 of 102 pts (34%) achieved a durable CR, with more than 65% of pts remaining in CR.