TY - JOUR
T1 - A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours
AU - Berlin, Jordan
AU - Ramanathan, Ramesh K.
AU - Strickler, John H.
AU - Subramaniam, Deepa S.
AU - Marshall, John
AU - Kang, Yoon Koo
AU - Hetman, Robert
AU - Dudley, Matthew W.
AU - Zeng, Jiewei
AU - Nickner, Caroline
AU - Xiong, Hao
AU - Komarnitsky, Philip
AU - Shepherd, Stacie Peacock
AU - Hurwitz, Herbert
AU - Lenz, Heinz Josef
N1 - Funding Information:
AbbVie provided financial support for this study (NCT01123876) and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. AbbVie and the authors thank the patients in this clinical trial and all study investigators for their contributions. Medical writing support was provided by Oana Draghiciu, PhD, TRM Oncology, The Hague, The Netherlands, funded by AbbVie. Results of this trial have partially been presented at ASCO, Chicago, IL, June 2014.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background: Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. Methods: Patients received veliparib (10-270 mg BID, days 1-5, 15-19) and FOLFIRI (days 1-3, 15-17) in three regimens containing 5-fluorouracil 2,400 mg/m2: irinotecan 150 mg/m2 and folinic acid 400 mg/m2 (part 1); irinotecan 180 mg/m2, folinic acid 400 mg/m2, and 5-fluorouracil 400 mg/m2 bolus (part 2), or irinotecan 180 mg/m2 (part 3). The RP2D was further evaluated in safety expansion cohorts. Preliminary antitumour activity was also assessed. Results: Ninety-two patients received ≥1 veliparib dose. MTD was not reached; RP2D was set at 200 mg BID veliparib plus FOLFIRI (without 5-fluorouracil bolus). Most common treatment-emergent adverse events were neutropenia (66.3%), diarrhoea, and nausea (60.9% each). Dose-limiting toxicities (n = 4) were grade 3 gastritis and grade 4 neutropenia and febrile neutropenia. Veliparib exposure was dose-proportional, with no effects on the pharmacokinetics of FOLFIRI components. Fifteen patients had a partial response (objective response rate, 17.6%). Conclusions: The acceptable safety profile and preliminary antitumour activity of veliparib plus FOLFIRI support further evaluation of this combination.
AB - Background: Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. Methods: Patients received veliparib (10-270 mg BID, days 1-5, 15-19) and FOLFIRI (days 1-3, 15-17) in three regimens containing 5-fluorouracil 2,400 mg/m2: irinotecan 150 mg/m2 and folinic acid 400 mg/m2 (part 1); irinotecan 180 mg/m2, folinic acid 400 mg/m2, and 5-fluorouracil 400 mg/m2 bolus (part 2), or irinotecan 180 mg/m2 (part 3). The RP2D was further evaluated in safety expansion cohorts. Preliminary antitumour activity was also assessed. Results: Ninety-two patients received ≥1 veliparib dose. MTD was not reached; RP2D was set at 200 mg BID veliparib plus FOLFIRI (without 5-fluorouracil bolus). Most common treatment-emergent adverse events were neutropenia (66.3%), diarrhoea, and nausea (60.9% each). Dose-limiting toxicities (n = 4) were grade 3 gastritis and grade 4 neutropenia and febrile neutropenia. Veliparib exposure was dose-proportional, with no effects on the pharmacokinetics of FOLFIRI components. Fifteen patients had a partial response (objective response rate, 17.6%). Conclusions: The acceptable safety profile and preliminary antitumour activity of veliparib plus FOLFIRI support further evaluation of this combination.
UR - http://www.scopus.com/inward/record.url?scp=85043363091&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85043363091&partnerID=8YFLogxK
U2 - 10.1038/s41416-018-0003-3
DO - 10.1038/s41416-018-0003-3
M3 - Article
C2 - 29527010
AN - SCOPUS:85043363091
VL - 118
SP - 938
EP - 946
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 7
ER -