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Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103)

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Abstract

Purpose

The primary objective of this study was to determine the recommended dose of the vascular disrupting agent, BNC105P, in combination with gemcitabine and carboplatin in patients with ovarian cancer in first or second relapse with a minimum 4 month progression-free interval after last platinum.

Methods

Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000 mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16 mg/m2 BNC105P on days 2 and 9 every 21 days for a maximum for six cycles. Maintenance treatment with 16 mg/m2 BNC105P treatment continued for a maximum of six additional cycles. Patients were followed for safety and anti-tumor activity.

Results

Fifteen patients were enrolled in the study. Adverse events were most commonly of hematological origin. Dose-limiting toxicities (thrombocytopenia and neutropenia) occurred in two patients at the dose level of 800 mg/m2 gemcitabine, carboplatin AUC4 and 16 mg/m2 BNC105P. No dose-limiting toxicities were observed at a dose level of gemcitabine 1000 mg/m2, carboplatin AUC4 and BNC105P 12 mg/m2. BNC105P as a single agent was well tolerated at a dose of 16 mg/m2 in maintenance treatment. Ten patients (67%) achieved a complete or partial response according to CA125 and/or RECIST response criteria, four of 13 (31%) responded by RECIST alone. The median progression-free survival was 5.9 months.

Conclusions

We have established that BNC105P 12 mg/m2 with gemcitabine 1000 mg/m2 and carboplatin AUC4 is the recommended dose level and has an acceptable toxicity profile. Further exploration of BNC105P in the ovarian cancer setting is planned.

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Acknowledgements

We thank Dave Cannon, NHMRC Clinical Trials Centre, for the administrative support during drafting and submission of the manuscript.

Funding

This trial was conducted by ANZGOG and HCRN with funding provided by Bionomics.

Author information

Authors and Affiliations

  1. NHMRC Clinical Trials Centre, Sydney, Australia

    Kristina Lindemann, Julie K. Martyn, Anneso S. Veillard, David Espinoza & Martin R. Stockler

  2. Division of Medicine, Department of Gynaecological Oncology, Oslo University Hospital, Oslo, Norway

    Kristina Lindemann

  3. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    Kristina Lindemann

  4. Chris O’Brien Lifehouse, Sydney, NSW, Australia

    Philip J. Beale

  5. Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, USA

    Emma Rossi

  6. Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia

    Jeff C. Goh

  7. Christchurch Hospital, Christchurch, New Zealand

    Michelle M. Vaughan

  8. Northside Hospital, University Gynecologic Oncology, Sandy Springs, USA

    Meaghan E. Tenney

  9. University of Chicago Medicine, Chicago, IL, USA

    Meaghan E. Tenney

  10. Academic Medical Centre, Amsterdam, The Netherlands

    Dirkje Sommeijer

  11. Flevohospital, Almere, The Netherlands

    Dirkje Sommeijer

  12. Apobiologix, Toronto, ON, M9L2Y6, Canada

    Jose L. Iglesias

  13. Bionomics Ltd, Thebarton, SA, Australia

    Gabriel Kremmidiotis, Jeremy Simpson, Elizabeth Doolin, Tina C. Lavranos & Annabell Leske

  14. Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, 3000, Australia

    Danny Rischin

  15. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

    Danny Rischin

Authors
  1. Kristina Lindemann
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  2. Philip J. Beale
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  3. Emma Rossi
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For ANZGOG and HCRN Collaborative Groups

Corresponding author

Correspondence to Danny Rischin.

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Conflict of interest

Dr. Lindemann, Dr. Veillard, Dr. Espinoza. Dr. Sommeijer, Dr. Rossi, Dr. Simpson, Dr. Tenney, Dr. Goh and Dr. Vaughan declare that they have nothing to disclose. Dr. Lavranos, Ms. Doolin, Ms. Leske and Dr. Kremmidiotis report salary/stakeholder from Bionomics Limited, outside the submitted work. Dr. Iglesias reports salary from Bionomics Limited, outside the submitted work and has a patent on BNC105 pending. Dr. Martyn reports Grants and non-financial support from Bionomics, during the conduct of the study. Dr. Beale reports personal fees from Roche, personal fees from Astra Zeneca, Grants from Roche, outside the submitted work. Dr. Rischin reports a Grant from Bionomics to ANZGOG for the research costs of the study; in addition, Dr. Rischin has a patent B55 (US) BNC105 Triple Combination Patent Application pending and trial steering/scientific advisory committees—Bionomics, Merck, Amgen, Regeneron, Bristol-Myers—all uncompensated. Dr. Stockler reports Grants from Bionomics, during the conduct of the study; Grants from Bayer, Grants from BMS, Grants from Astra Zeneca, Grants from Specialised Therapeutics, Grants from Amgen, Grants from Astellas, Grants from Merck, outside the submitted work.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Lindemann, K., Beale, P.J., Rossi, E. et al. Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103). Cancer Chemother Pharmacol 83, 97–105 (2019). https://doi.org/10.1007/s00280-018-3706-5

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  • DOI: https://doi.org/10.1007/s00280-018-3706-5

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