33524-65

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

Subcategory: 
Category: 
Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Clinical Science Symposium, New Agents for Lymphoma
Abstract Number: 

8500

Citation: 
J Clin Oncol 27:15s, 2009 (suppl; abstr 8500)
Author(s): 
N. Bartlett, A. Forero-Torres, J. Rosenblatt, M. Fanale, S. J. Horning, S. Thompson, E. L. Sievers, D. A. Kennedy; Washington University Siteman Cancer Center, St. Louis, MO; University of Alabama at Birmingham, Birmingham, AL; University Miami Sylvester Comprehensive Cancer Center, Miami, FL; University of Texas M.D. Anderson Cancer Center, Houston, TX; Stanford University, Stanford, CA; Seattle Genetics, Inc., Bothell, WA

Abstract Disclosures

Abstract: 

Background: A defining feature of HL and sALCL is CD30 expression on malignant cells. The ADC SGN-35 comprises an anti-CD30 antibody conjugated to the antitubulin agent monomethyl auristatin E (MMAE). SGN-35 causes cell cycle arrest and apoptosis by binding to CD30 on the tumor cell surface, internalizing, and releasing MMAE into the cell. In a previous phase 1 study with q3 wk dosing, 54% of pts achieved an objective response (CR/PR) at SGN-35 doses ≥1.2 mg/kg [ASH 2008 abstract 1006]. Methods: To assess if more frequent dosing might maximize anti-tumor activity with acceptable tolerability, a multicenter, phase 1, weekly dosing, dose-escalation study (3+3 design) was conducted in pts with refractory or recurrent HL or sALCL. SGN-35 was administered weekly at doses of 0.4-1 mg/kg (2-hr IV infusions). Pts with stable disease or better (Cheson 2007) after two 28-day cycles (6 doses) were eligible to continue SGN-35 treatment. Results: In 17 pts, median age was 38 yrs (range 25-67). Pts received a median of 4 prior therapies; 65% received an autologous SCT. MTD has not been defined. One related G3 event (diarrhea) and no related G4 events occurred. The most common related adverse events were G1/G2 rash, nausea, and peripheral neuropathy. Exposure to SGN-35 (AUC) increased relative to dose level. Multiple CRs were observed at higher doses (table); observed time to response in the 1 mg/kg dose group was approximately 8 wks. The 7 pts with CRs all remain on treatment. Enrollment to SGN-35 monotherapy continues at 1.2 mg/kg; combination therapy will be subsequently explored. Conclusions: SGN-35 was generally well tolerated and induced CRs in 7 of 8 evaluable pts at the two highest doses in heavily pretreated patients. Pivotal trials of this antibody-drug conjugate will initiate in early 2009.
 


Dose (mg/kg) N CR PR SD PDNot Evaluable

0.44004*00
0.6301110
0.843*0010
1.064**0002†
Total1771522

Each * = 1 sALCL pt; all others are HL. † 1 pt withdrawn after Cycle 1 had PR assessed at EOT.