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A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer

  • PHASE I STUDIES
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Summary

Background Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish the recommended phase II dose (RP2D) and response rate of panitumumab, an EGFRi, plus BKM120, a PI3K inhibitor, in advanced CRC. Methods Patients with chemotherapy refractory KRAS wt CRC, who were EGFRi naive were enrolled. A 3 + 3 dose escalation design was utilized. The starting dose of panitumumab was 6 mg/kg iv every 2 weeks with BKM120 at 60 mg oral daily. Results Nineteen patients were treated and 17 were evaluable for response. The starting dose was not tolerable (mucositis, fatigue). At dose level (DL) 1, three of six patients discontinued treatment due to toxicity, DL − 1 had no significant toxicity. Panitumumab 6 mg/kg iv q 2 weeks with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. One patient (5.9%) who was PTEN and PIK3CA negative by IHC had a partial response, seven had stable disease, and nine had disease progression. Conclusion Panitumumab (6 mg/kg iv q 2 weeks) with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. Toxicities including fatigue, rash and mucositis. There was little evidence of activity in this biomarker unselected cohort.

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Funding

CCTG is supported by the Canadian Cancer Society Research Institute to the Canadian Cancer Trials Group (grant #021039).

This study was carried out by the Canadian Cancer Trials Group. Novartis provided BKM120 and partial financial support for the trial.

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Authors and Affiliations

  1. Ottawa Hospital Research Institute, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, K1H 8L6, Canada

    Rachel Goodwin, Derek Jonker, Michael Vickers & Caryn Bohemier

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Michael Cabanero & Ming-Sound Tsao

  3. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Eric Chen

  4. Virginia Mason Cancer Institute, Seattle, WA, USA

    Hagen Kennecke

  5. BCCA-Vancouver Centre, Vancouver, BC, Canada

    Howard Lim

  6. Canadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada

    Heather Ritter, Dongsheng Tu & Lesley Seymour

Authors
  1. Rachel Goodwin
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  2. Derek Jonker
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  3. Eric Chen
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  4. Hagen Kennecke
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  5. Michael Cabanero
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  6. Ming-Sound Tsao
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  7. Michael Vickers
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  8. Caryn Bohemier
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  9. Howard Lim
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  10. Heather Ritter
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  11. Dongsheng Tu
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  12. Lesley Seymour
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Corresponding author

Correspondence to Rachel Goodwin.

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Conflict of interest

R Goodwin: Honorarium Novartis, Honorarium Amgen.

D Jonker: No conflicts of interest.

E. Chen: No conflicts of Interest.

H Kennecke: No Conflicts of Interest.

M Cabanero: No conflicts of Interest.

M Tsao: No conflicts of interest.

M Vickers: No Conflicts of Interest.

C Bohemier: No Conflicts of Interest.

H Lim: No conflicts of Interest.

H Ritter: No Conflicts of Interest.

D Tu: No Conflicts of Interest.

L Seymour: Funding to support conduct of the trial.

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

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Goodwin, R., Jonker, D., Chen, E. et al. A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer. Invest New Drugs 38, 1077–1084 (2020). https://doi.org/10.1007/s10637-019-00814-3

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  • DOI: https://doi.org/10.1007/s10637-019-00814-3

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