Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC) Journal Article

Authors: Abou-Alfa, G. K.; Yen, C. J.; Hsu, C. H.; O'Donoghue, J.; Beylergil, V.; Ruan, S.; Pandit-Taskar, N.; Gansukh, B.; Lyashchenko, S. K.; Ma, J.; Wan, P.; Shao, Y. Y.; Lin, Z. Z.; Frenette, C.; O’Neil, B.; Schwartz, L.; Smith-Jones, P. M.; Ohtomo, T.; Tanaka, T.; Morikawa, H.; Maki, Y.; Ohishi, N.; Chen, Y. C.; Agajanov, T.; Boisserie, F.; Di Laurenzio, L.; Lee, R.; Larson, S. M.; Cheng, A. L.; Carrasquillo, J. A.
Article Title: Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC)
Abstract: Purpose: Codrituzumab, a humanized antibody against glypican-3, is highly expressed in HCC. A phase I study evaluated the combination with sorafenib in HCC. Patients and methods: In a 3 + 3 design, codrituzumab was given intravenously in various doses with sorafenib 400 mg twice daily to patients with advanced HCC, age ≥18, ECOG 0–1, Child-Pugh A and B7, adequate organ functions, and no prior systemic therapy, with tumor assessment by RECIST 1.0 and safety by CTCAE 3.0. PK and pre, during, and post-therapy 124I radiolabeled codrituzumab PET scan imaging were performed. Results: 41 patients were enrolled: 2.5 mg/kg weekly (qw) (12), 5 mg/kg qw (12), 10 mg/kg qw (3), 1600 mg every 2 weeks (q2w) (6), and 1600 mg qw (7). Two drug limiting toxicities occurred: grade 3 hyponatremia at 5 mg/kg and grade 3 hyponatremia and hyperglycemia at 1600 mg q2w. Adverse events occurred in 80% of patients, including at least one ≥grade 3: ten (25%) increased AST, three (7.5%) increased ALT, and ten (25%) increased lipase. There were no responses and nine (25.7%) had stable disease. PK Cmax and AUCt of codrituzumab and sorafenib were comparable to single-agent data. Thirteen out of 14 patients showed 124I radiolabeled codrituzumab uptake in tumor. In all three patients who underwent a post-progression PET, glypican-3 remained expressed. Conclusion: Codrituzumab plus sorafenib were tolerated at 1600 mg q2w and 400 mg bid, respectively, with no responses. Codrituzumab exerts selective distribution to HCC cells, and GPC3 does not show any down-regulation post-progression (NCT00976170). © 2017, Springer-Verlag Berlin Heidelberg.
Journal Title: Cancer Chemotherapy and Pharmacology
Volume: 79
Issue: 2
ISSN: 0344-5704
Publisher: Springer  
Date Published: 2017-02-01
Start Page: 421
End Page: 429
Language: English
DOI: 10.1007/s00280-017-3241-9
PROVIDER: scopus
PUBMED: 28120036
PMCID: PMC5548107
Notes: Article -- Export Date: 2 March 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Ghassan Abou-Alfa
    385 Abou-Alfa
  2. Shutian Ruan
    50 Ruan
  3. Steven M Larson
    908 Larson
  4. Bolorsukh Gansukh
    15 Gansukh
  5. Jennifer Ma
    39 Ma
  6. Peter Justin Wan
    11 Wan