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ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.

Publication ,  Conference
Wainberg, ZA; Wang, L; Yue, H; Motwani, M; Kasichayanula, S; Blaney, ME; Naumovski, L; Strickler, JH
Published in: Journal of Clinical Oncology
February 1, 2019

TPS720 Background: Dual variable domain immunoglobulin ABT-165 targets human vascular endothelial growth factor (VEGF) and delta-like ligand 4 (DLL4). Combined VEGF and DLL4 blockade increased inhibition of subcutaneous xenograft growth of human colon cancer-derived cell lines versus blockade of either axis alone. In vivo, ABT-165 plus chemotherapy (CT) induced tumor regression with improved efficacy, vs anti-VEGF monoclonal antibody plus CT. In a phase 1 study, tolerable recommended phase 2 dose was identified for ABT-165 plus FOLFIRI and showed promising efficacy. This phase 2 trial in progress assesses efficacy/safety of ABT-165 plus FOLFIRI vs bevacizumab (bev) plus FOLFIRI in patients with second-line mCRC. Methods: This is an open-label, multicenter, phase 2 randomized (1:1) trial (NCT03368859) in patients (≥ 18 years; Eastern Cooperative performance status: 0–1) with histologically/cytologically confirmed mCRC who progressed after fluoropyrimidine/oxaliplatin and bev. ABT-165 (2.5 mg/kg) plus FOLFIRI (irinotecan: 180 mg/m; leucovorin: 400 mg/m; fluorouracil bolus: 400 mg/m, infusion: 2400 mg/m) or bev (5 mg/kg) plus FOLFIRI are given intravenously on day 1 of each 14-day cycle, until disease progression/intolerable toxicity. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), and safety. Exploratory endpoints include biomarkers predictive for efficacy/safety, correlation of DLL4 levels with PFS, OS, and ORR, pharmacodynamic effects, and efficacy/safety-exposure relationships in ABT-165 arm. Hazard ratios of PFS and OS comparing the 2 groups are estimated using Cox proportional hazard model. Kaplan-Meier methodology is used to estimate PFS and OS curves, median PFS and OS, and their 90% confidence intervals. Safety is assessed by ABT-165 exposure, adverse events (AEs), serious AEs, all deaths, and changes in laboratory data and vital signs. Archival tissue is collected and evaluated for DLL4 expression and angiogenesis signature. Approximately 100 patients are planned to be enrolled, with recruitment initiated January 2018. Clinical trial information: NCT03368859.

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Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2019

Volume

37

Issue

4_suppl

Start / End Page

TPS720 / TPS720

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Chicago
ICMJE
MLA
NLM
Wainberg, Z. A., Wang, L., Yue, H., Motwani, M., Kasichayanula, S., Blaney, M. E., … Strickler, J. H. (2019). ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab. In Journal of Clinical Oncology (Vol. 37, pp. TPS720–TPS720). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2019.37.4_suppl.tps720
Wainberg, Zev A., Lan Wang, Huibin Yue, Monica Motwani, Sreeneeranj Kasichayanula, Martha Elizabeth Blaney, Louie Naumovski, and John H. Strickler. “ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.” In Journal of Clinical Oncology, 37:TPS720–TPS720. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.4_suppl.tps720.
Wainberg ZA, Wang L, Yue H, Motwani M, Kasichayanula S, Blaney ME, et al. ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. TPS720–TPS720.
Wainberg, Zev A., et al. “ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab.Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. TPS720–TPS720. Crossref, doi:10.1200/jco.2019.37.4_suppl.tps720.
Wainberg ZA, Wang L, Yue H, Motwani M, Kasichayanula S, Blaney ME, Naumovski L, Strickler JH. ABT-165 plus FOLFIRI versus bevacizumab plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine/oxaliplatin and bevacizumab. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. TPS720–TPS720.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2019

Volume

37

Issue

4_suppl

Start / End Page

TPS720 / TPS720

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences