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A phase I and pharmacokinetic study of afilbercept with FOLFIRI: comparison of Chinese and Caucasian populations

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Summary

Background This study assessed the preliminary safety, pharmacokinetics (PK) and anti-tumor effects of aflibercept in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in Chinese patients with previously-treated advanced solid malignancies. Patients and Methods This open-label single-arm Phase I study conducted at two centers in China included adult (≥18 years) patients with metastatic or unresectable solid malignancies who had received ≥1 prior treatment. Patients received aflibercept 4 mg/kg IV on Day 1 followed by FOLFIRI over Days 1 and 2 every 2 weeks, and were assessed for safety, tumor response, PK parameters and immunogenicity. Post-hoc analyses included calculation of progression-free survival (PFS) for patients with colorectal cancer (CRC). Results A total of 20 patients were enrolled. The most common Grade 3/4 adverse events included neutropenia (35%), hypertension (30%), stomatitis (20%) and proteinuria (20%), and no anti-aflibercept antibodies were detected. Six patients achieved a partial response, and in 15 patients with CRC median PFS was 5.95 months (95% CI: 5.29–8.77). Free aflibercept remained in excess of VEGF-bound aflibercept for the majority of the study treatment duration. The mean free aflibercept values for Cmax (64.8 μg/mL) AUC (291 μg.day/mL), CL (0.92 L/day) and Vss (5.9 L) were similar to those measured in Caucasian patients. The addition of aflibercept did not influence the PK of the chemotherapy agents. Conclusion For Chinese patients with pre-treated advanced solid malignancies, 4 mg/kg of aflibercept in combination with FOLFIRI was well-tolerated, demonstrated preliminary anti-tumor activity and had a PK profile consistent with that in Caucasian patients.

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Acknowledgements

This study was sponsored by Sanofi (China). Editorial support for this manuscript was paid for by Sanofi and provided by Anne Wong at Adelphi Consultech.

Author contributions

All authors contributed to the study concept, design, conduct and interpretation of data. Ruihua Xu, Jianming Xu, Dongsheng Zhang and Rongrui Liu were responsible for data collection. Xing Sun provided statistical analysis and interpretation. All authors helped to draft and provide critical input into this manuscript, and approved the final version for publication.

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Authors and Affiliations

  1. Affiliated Hospital Cancer Center (307th Hospital of Chinese People’s Liberation Army), Academy of Military Medical Sciences, No. 8 East St, Fengtai, Beijing, China

    Jianming Xu & Rongrui Liu

  2. Sanofi R&D China, 2F, No. 108, Jian Guo Lu, Chaoyang District, Beijing, 100022, China

    Yingxin Li & Fengying Xue

  3. Sanofi R&D US, 55 Corporate Dr, Bridgewater, NJ, 08807, USA

    Xing Sun

  4. Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Yuexiu, Guangzhou, Guangdong, China

    Dongsheng Zhang & Ruihua Xu

  5. Sanofi R&D France, 3 digue d’Alfortville, 94140, Alfortville, France

    Samira Ziti-Ljajic

  6. Sanofi R&D Asia Pacific, 2F, No. 108, Jian Guo Lu, Chaoyang District, Beijing, 100022, China

    Dongmei Shi

  7. Sanofi R&D Asia Pacific, 1 avenue Pierre Brossolette, 91385, Chilly-Mazarin, France

    Nathalie Le bail

Authors
  1. Jianming Xu
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  2. Yingxin Li
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  3. Xing Sun
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  4. Dongsheng Zhang
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  5. Rongrui Liu
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  6. Samira Ziti-Ljajic
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  7. Dongmei Shi
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  8. Fengying Xue
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  9. Nathalie Le bail
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  10. Ruihua Xu
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Corresponding author

Correspondence to Ruihua Xu.

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Conflicts of interest

Yingxin Li, Xing Sun, Samira Ziti-Ljajic, Dongmei Shi and Nathalie Le bail are employees of Sanofi. The other authors have no further conflicts of interest to declare.

Funding

This study was sponsored by Sanofi (China). Editorial support for this manuscript was paid for by Sanofi and provided by Anne Wong at Adelphi Consultech.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Xu, J., Li, Y., Sun, X. et al. A phase I and pharmacokinetic study of afilbercept with FOLFIRI: comparison of Chinese and Caucasian populations. Invest New Drugs 35, 463–470 (2017). https://doi.org/10.1007/s10637-016-0421-0

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  • DOI: https://doi.org/10.1007/s10637-016-0421-0

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