A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours

Jordan Berlin, Ramesh K. Ramanathan, John H. Strickler, Deepa S. Subramaniam, John Marshall, Yoon Koo Kang, Robert Hetman, Matthew W. Dudley, Jiewei Zeng, Caroline Nickner, Hao Xiong, Philip Komarnitsky, Stacie Peacock Shepherd, Herbert Hurwitz, Heinz Josef Lenz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)938-946
Number of pages9
JournalBritish journal of cancer
Issue number7
StatePublished - Apr 1 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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