Interim analysis of a phase 1, open-label, dose-escalation study of SGN-CD19A in patients with relapsed or refractory B-lineage non-Hodgkin lymphoma (NHL).

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Oral Abstract Session, Lymphoma
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8505)
Andres Forero-Torres, Craig Moskowitz, Ranjana H. Advani, Bijal D. Shah, Ana Kostic, Tina M. Albertson, Larissa Sandalic, Baiteng Zhao, Michelle A. Fanale; The University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Memorial Sloan Kettering Cancer Center, New York, NY; Stanford University Medical Center, Stanford, CA; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Seattle Genetics, Inc., Bothell, WA; The University of Texas MD Anderson Cancer Center, Houston, TX

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Abstract Disclosures


Background: CD19, a member of the immunoglobulin superfamily, is expressed in most patients with B-cell NHL. SGN-CD19A is a novel antibody-drug conjugate composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a maleimidocaproyl linker. Methods: This phase 1, open-label, dose-escalation study investigates the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-CD19A in patients with relapsed or refractory B-cell NHL with at least 1 prior systemic regimen (NCT01786135). Patients with DLBCL or follicular lymphoma grade 3 (FL3) must have received intensive salvage therapy. A modified continual reassessment method is used for dose allocation and maximum tolerated dose (MTD) estimation. SGN-CD19A is given by IV on Day 1 of 21-day cycles. Results: To date, 22 patients with a median age of 63 years (range, 33 to 81) with DLBCL (18), MCL (3), and FL3 (1) have been treated with SGN-CD19A. 50% of patients were refractory to their last treatment; 6 patients received prior autologous SCT. Patients have received a median of 2 cycles (range, 1 to 9) at dose levels from 0.5 mg/kg to 6 mg/kg. 11 patients remain on treatment and 11 have discontinued due to progressive disease (10) and patient decision (1). No dose-limiting toxicity (DLT) has been reported in 21 DLT-evaluable patients; the MTD has not yet been identified. Adverse events occurring in ≥10% of patients are fatigue (27%), blurred vision (27%), dry eye (23%), constipation (23%), dyspnea (14%), and keratitis (14%). Of the 20 patients evaluated, objective responses were observed in 8 patients (40%), 6 CRs (30%) and 2 PRs (10%); 3 patients had SD (15%) and 9 had PD (45%). SGN-CD19A ADC plasma exposures were approximately dose-proportional in preliminary PK analysis with mean terminal half-lives between 9-30 days. Conclusions: To date, SGN-CD19A has shown evidence of clinical activity with an objective response rate of 40% (8 of 20 patients) and an observed CR rate of 30% (6 of 20 patients). No DLTs have been reported in tested dose levels; enrollment is ongoing to identify the optimal dose of SGN-CD19A for future studies. Clinical trial information: NCT01786135.