TY - JOUR
T1 - A phase I study of ADCT-402 (loncastuximab tesirine), a novel pyrrolobenzodiazepine-based antibody–drug conjugate, in relapsed/ refractory B-cell non-Hodgkin lymphoma
AU - Kahl, Brad S.
AU - Hamadani, Mehdi
AU - Radford, John
AU - Carlo-Stella, Carmelo
AU - Caimi, Paolo
AU - Reid, Erin
AU - Feingold, Jay M.
AU - Ardeshna, Kirit M.
AU - Solh, Melhem
AU - Heffner, Leonard T.
AU - Ungar, David
AU - He, Shui
AU - Boni, Joseph
AU - Havenith, Karin
AU - O'Connor, Owen A.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Purpose: ADCT-402 (loncastuximab tesirine) is an antibody–drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL). Patients and Methods: A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages 18 years with relapsed/refractory (R/R) B-cell NHL. Patients received loncastuximab tesirine every 3 weeks at doses assigned by a 3þ3 dose-escalation design. Dose escalation was used to assess the safety and tolerability of loncastuximab tesirine to determine the dose for expansion. Secondary objectives evaluated clinical activity, characterized the pharmacokinetic profile, and evaluated antidrug antibodies. Results: During dose escalation, 88 patients with R/R B-cell NHL were treated with loncastuximab tesirine at doses 15 to 200 mg/kg. Treatment-emergent adverse events (TEAEs) were experienced by 87/88 (98.9%) patients. Most common TEAEs (20% of patients) were hematologic abnormalities, fatigue, edema, liver test abnormalities, nausea, rash, and dyspnea. Grade 3 TEAEs (5% of patients) included hematologic abnormalities, liver test abnormalities, fatigue, and dyspnea. Overall response rate at doses 120 mg/kg was 59.4% (41 of 69 patients; 40.6% complete response; 18.8% partial response). Median duration of response, progression-free survival, and overall survival (all doses) were 4.8, 5.5, and 11.6 months, respectively. Drug exposure increased with increasing dose, showing moderate accumulation with multiple doses 150 mg/kg. There was no evidence of immunogenicity. Conclusions: Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study. A phase II study with initial dosing at 150 mg/kg has been initiated based on these results.
AB - Purpose: ADCT-402 (loncastuximab tesirine) is an antibody–drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL). Patients and Methods: A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages 18 years with relapsed/refractory (R/R) B-cell NHL. Patients received loncastuximab tesirine every 3 weeks at doses assigned by a 3þ3 dose-escalation design. Dose escalation was used to assess the safety and tolerability of loncastuximab tesirine to determine the dose for expansion. Secondary objectives evaluated clinical activity, characterized the pharmacokinetic profile, and evaluated antidrug antibodies. Results: During dose escalation, 88 patients with R/R B-cell NHL were treated with loncastuximab tesirine at doses 15 to 200 mg/kg. Treatment-emergent adverse events (TEAEs) were experienced by 87/88 (98.9%) patients. Most common TEAEs (20% of patients) were hematologic abnormalities, fatigue, edema, liver test abnormalities, nausea, rash, and dyspnea. Grade 3 TEAEs (5% of patients) included hematologic abnormalities, liver test abnormalities, fatigue, and dyspnea. Overall response rate at doses 120 mg/kg was 59.4% (41 of 69 patients; 40.6% complete response; 18.8% partial response). Median duration of response, progression-free survival, and overall survival (all doses) were 4.8, 5.5, and 11.6 months, respectively. Drug exposure increased with increasing dose, showing moderate accumulation with multiple doses 150 mg/kg. There was no evidence of immunogenicity. Conclusions: Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study. A phase II study with initial dosing at 150 mg/kg has been initiated based on these results.
UR - http://www.scopus.com/inward/record.url?scp=85075960499&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-0711
DO - 10.1158/1078-0432.CCR-19-0711
M3 - Article
C2 - 31685491
AN - SCOPUS:85075960499
SN - 1078-0432
VL - 25
SP - 6986
EP - 6994
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -