TY - JOUR
T1 - Phase I trial of toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non-Hodgkin's lymphoma
AU - Leonard, John P.
AU - Link, Brian K.
AU - Emmanouilides, Christos
AU - Gregory, Stephanie A.
AU - Weisdorf, Daniel
AU - Andrey, Jeffrey
AU - Hainsworth, John
AU - Sparano, Joseph A.
AU - Tsai, Donald E.
AU - Horning, Sandra
AU - Krieg, Arthur M.
AU - Weiner, George J.
PY - 2007/10/15
Y1 - 2007/10/15
N2 - Purpose: PF-3512676 (formerly CpG 7909) is a novel Toll-like receptor 9-activating oligonucleotide with single-agent antitumor activity that augments preclinical rituximab efficacy. This Phase I trial was designed to investigate the safety, tolerability, and preliminary antitumor activity of PF-3512676 in combination with rituximab. Experimental Design: Patients with relapsed/refractory CD20+ B cell non-Hodgkin's lymphoma received i.v. rituximab (375 mg/m2/week for 4 weeks) and PF-3512676 weekly for 4 weeks either i.v. (0.04, 0.16, 0.32, or 0.48 mg/kg) or s.c. (0.01, 0.04, 0.08, or 0.16 mg/kg). An additional extended-treatment cohort received 4 weeks of 0.24 mg/kg s.c. PF-3512676 in combination with rituximab followed by s.c. PF-3512676 alone weekly for 20 weeks. Results: Patients (N = 50) had received a median of three prior therapies (range, 1-11) including rituximab in 80% of patients. Treatment-related adverse events occurred in 11 of 19 (58%) i.v. patients, 15 of 19 (79%) s.c. patients, and all 12 patients in the extended-treatment cohort. Most common adverse events were mild to moderate systemic flu-like symptoms and injection-site reactions (s.c. cohorts only). Grade 3/4 neutropenia occurred in four patients. Objective responses occurred in 12 of 50 (24%) patients overall and in 6 of 12 (50%) patients in the extended-treatment cohort, including 2 patients with rituximab-refractory disease. Conclusion: Brief or extended-duration PF-3512676 can be safely administered in combination with rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.
AB - Purpose: PF-3512676 (formerly CpG 7909) is a novel Toll-like receptor 9-activating oligonucleotide with single-agent antitumor activity that augments preclinical rituximab efficacy. This Phase I trial was designed to investigate the safety, tolerability, and preliminary antitumor activity of PF-3512676 in combination with rituximab. Experimental Design: Patients with relapsed/refractory CD20+ B cell non-Hodgkin's lymphoma received i.v. rituximab (375 mg/m2/week for 4 weeks) and PF-3512676 weekly for 4 weeks either i.v. (0.04, 0.16, 0.32, or 0.48 mg/kg) or s.c. (0.01, 0.04, 0.08, or 0.16 mg/kg). An additional extended-treatment cohort received 4 weeks of 0.24 mg/kg s.c. PF-3512676 in combination with rituximab followed by s.c. PF-3512676 alone weekly for 20 weeks. Results: Patients (N = 50) had received a median of three prior therapies (range, 1-11) including rituximab in 80% of patients. Treatment-related adverse events occurred in 11 of 19 (58%) i.v. patients, 15 of 19 (79%) s.c. patients, and all 12 patients in the extended-treatment cohort. Most common adverse events were mild to moderate systemic flu-like symptoms and injection-site reactions (s.c. cohorts only). Grade 3/4 neutropenia occurred in four patients. Objective responses occurred in 12 of 50 (24%) patients overall and in 6 of 12 (50%) patients in the extended-treatment cohort, including 2 patients with rituximab-refractory disease. Conclusion: Brief or extended-duration PF-3512676 can be safely administered in combination with rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.
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U2 - 10.1158/1078-0432.CCR-07-0815
DO - 10.1158/1078-0432.CCR-07-0815
M3 - Article
C2 - 17947483
AN - SCOPUS:35948987594
SN - 1078-0432
VL - 13
SP - 6168
EP - 6174
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -