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Targeted Oncology

, Volume 14, Issue 5, pp 541–550 | Cite as

Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial

  • Ali A. Mokdad
  • Hao Zhu
  • Muhammad S. Beg
  • Yull Arriaga
  • Jonathan E. Dowell
  • Amit G. Singal
  • Adam C. YoppEmail author
Original Research Article

Abstract

Background

Bavituximab, an immunomodulator, targets phosphatidylserine (PS), a membrane lipid externalized on tumor and endothelial cells in response to sorafenib.

Objective

The objective of this phase II study was to assess the efficacy of combination bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC).

Methods

In this single-arm phase II study, patients with HCC determined to be unresectable with Eastern Cooperative Oncology Group (ECOG) score ≤ 2, Child–Pugh score A/B7 received intravenous bavituximab 3 mg/kg weekly and oral sorafenib 400 mg twice daily until disease progression or intolerable toxicity. We investigated time to progression (TTP) for patients receiving combination bavituximab and sorafenib compared with that for sorafenib-only historical controls.

Results

In total, 38 patients were accrued. The median follow-up was 6.1 months. Patient characteristics were as follows: median age 61 years; male 82%; hepatitis C virus 79%; Black 39%, Hispanic 26%, White 29%; previous treatment 39%; macrovascular invasion 84%; and extrahepatic metastases 24%. The median TTP was 6.7 months (95% confidence interval [CI] 4–17). The median overall survival was 6.1 months (95% CI 5–8), and the median disease-specific survival was 8.6 months (95% CI 6–14). Two patients experienced partial responses; none had a complete response. The disease control rate was 58%. Treatment-related adverse events were observed in 63% of patients, with the most commonly reported therapy-related symptoms being diarrhea (32%), fatigue (26%), and anorexia (24%).

Conclusions

The efficacy of adding bavituximab to sorafenib for the treatment of advanced HCC was inconclusive; however, the combination regimen did not exacerbate toxicities associated with single-agent sorafenib.

ClinicalTrials.gov identifier

NCT01264705.

Notes

Compliance with Ethical Standards

Funding

This work was supported by Peregrine Pharmaceuticals, Inc.

Conflict of interest

AAM, HZ, YA, JD, and ACY have no conflicts of interest that might be relevant to the contents of this manuscript. MSB has served in a consulting/advisory role for Cegene, Ipsen, Genentech/Roche, Guardant Health, and Boston Biomedical; on a speaker’s bureau for Ipsen, Genentech/Roche, and Bristol-Myers Squibb; and has received research funding from Gelgene, Bristol-Myers Squibb, AstraZeneca/MedImmune, Merk Serono, Agios, Five Prime Therapeutics, MedImuune, Tolero Pharmaceuticals, ArQule, Genetech, Sillajen, and CASI Pharmaceuticals. AGS has served in a consultant/advisory role for Eisai, Exelixis, Bayer, and BMS and on a speaker’s bureau for Bayer and BMS.

Supplementary material

11523_2019_663_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ali A. Mokdad
    • 1
  • Hao Zhu
    • 2
  • Muhammad S. Beg
    • 2
  • Yull Arriaga
    • 2
  • Jonathan E. Dowell
    • 2
  • Amit G. Singal
    • 3
  • Adam C. Yopp
    • 1
    Email author
  1. 1.Department of Surgery, Division of Surgical OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Medicine, Division of Medical OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of Medicine, Division of Digestive and Liver DiseasesUniversity of Texas Southwestern Medical CenterDallasUSA

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