TY - JOUR
T1 - Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma
AU - Hamadani, Mehdi
AU - Radford, John
AU - Carlo-Stella, Carmelo
AU - Caimi, Paolo F.
AU - Reid, Erin
AU - O'Connor, Owen A.
AU - Feingold, Jay M.
AU - Ardeshna, Kirit M.
AU - Townsend, William
AU - Solh, Melhem
AU - Heffner, Leonard T.
AU - Ungar, David
AU - Wang, Luqiang
AU - Boni, Joseph
AU - Havenith, Karin
AU - Qin, Yajuan
AU - Kahl, Brad S.
N1 - Funding Information:
This study was supported by ADC Therapeutics, which also funded the Fishawack Communications, Ltd, editorial assistance. K.M.A. is supported by the University College London (UCL)/UCL Hospitals Biomedical Research Unit.
Funding Information:
Editorial assistance was provided by Becky Salisbury and Louise Gildea at Fishawack Communications, Ltd. This study was supported by ADC Therapeutics, which also funded the Fishawack Communications, Ltd, editorial assistance. K.M.A. is supported by the University College London (UCL)/UCL Hospitals Biomedical Research Unit. All authors meet the International Committee of Medical Journal Editors criteria for authorship and take responsibility for the integrity of the work as a whole. They also had full access to the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.
Funding Information:
Conflict-of-Interest disclosure: M.H. has received research support from Takeda Pharmaceutical Company, Spectrum Pharmaceuticals, and Astellas Pharma; has served as a consultant for Janssen R&D, Incyte Corporation, ADC Therapeutics, Celgene Corporation, Pharmacyclics, Omeros, AbGenomics, Verastem, and TeneoBio; and has participated in speakers' bureau for Sanofi Genzyme and AstraZeneca. J.R. has acted in a consultant/advisory role for Takeda, ADC Therapeutics, Bristol-Myers Squibb, Novartis, and Kite Pharma; has been a speaker for Takeda, ADC Therapeutics, and Seattle Genetics; has received research funding from Takeda; has provided expert testimony for Takeda and ADC Therapeutics; and holds stocks/shares in AstraZeneca and GlaxoSmithKline (spouse). C.C.-S. has received research support from ADC Therapeutics and Rhizen Pharmaceuticals; has served as a consultant or advisor for Servier, Novartis, Genenta Science srl, ADC Therapeutics, Roche, Boehringer Ingelheim, and Sanofi; and has received honoraria for speaker engagements from Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, and AstraZeneca. P.F.C., E.R., O.A.O., and M.S. have received research support from ADC Therapeutics. K.M.A. has received honoraria from or attended advisory boards for Celgene, Gilead, Takeda, Roche, and Beigene. W.T. has received research support from ADC Therapeutics and honoraria from Roche and Gilead. L.T.H. has received institutional research funding from Pharmacyclics, Genentech, Kite, and ADC Therapeutics and an honorarium from Kite. B.S.K. has received research support from ADC Therapeutics and acted as a consultant for Seattle Genetics and Genentech. J.M.F., D.U., L.W., J.B., K.H., and Y.Q. are employees of ADC Therapeutics with stock options.
Publisher Copyright:
© 2021 American Society of Hematology
PY - 2021/5/13
Y1 - 2021/5/13
N2 - The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3 + 3 dose escalation at 15 to 200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CRs). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved a CR. Loncastuximab tesirine had good stability in serum, notable antitumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for phase 2 was determined as 150 µg/kg every 3 weeks for 2 doses followed by 75 µg/kg every 3 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02669017.
AB - The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3 + 3 dose escalation at 15 to 200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CRs). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved a CR. Loncastuximab tesirine had good stability in serum, notable antitumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for phase 2 was determined as 150 µg/kg every 3 weeks for 2 doses followed by 75 µg/kg every 3 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02669017.
UR - http://www.scopus.com/inward/record.url?scp=85106521180&partnerID=8YFLogxK
U2 - 10.1182/blood.2020007512
DO - 10.1182/blood.2020007512
M3 - Article
C2 - 33211842
AN - SCOPUS:85106521180
SN - 0006-4971
VL - 137
SP - 2634
EP - 2645
JO - Blood
JF - Blood
IS - 19
ER -