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Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial)

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Abstract

Purpose

To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.

Methods

Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.

Results

Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.

Conclusions

Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.

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Acknowledgments

This study was funded by Pharma Mar, S.A. The study was supported at the Glasgow Centre by the Experimental Cancer Medicine Centre (ECMC), funded by Cancer Research UK and the Chief Scientist Office, Scotland. R.D. Petty’s current affiliation is Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom. B. Miguel-Lillo’s current affiliation is SGS Exprimo NV, Mechelen, Belgium.  

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Authors and Affiliations

  1. Aberdeen Royal Infirmary, Aberdeen, UK

    Russell Petty

  2. St James University Hospital, Leeds, UK

    Alan Anthoney

  3. Centre Hospitalier Universitaire Morvan, Brest, France

    Jean-Philippe Metges

  4. Hospital Vall d’Hebron, Barcelona, Spain

    Maria Alsina

  5. Institut Paoli Calmettes, Marseille, France

    Anthony Gonçalves

  6. The Beatson West of Scotland Cancer Centre, Glasgow, UK

    Jennifer Brown

  7. Hospital del Mar, Barcelona, Spain

    Clara Montagut

  8. Centre François Baclesse, Caen, France

    Katharina Gunzer

  9. PharmaMar Clinical R&D, Colmenar Viejo, Madrid, Spain

    Gianluca Laus, Jorge Luis Iglesias Dios, Bernardo Miguel-Lillo & Patrick Bohan

  10. Institut Català d’Oncologia (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain

    Ramón Salazar

Authors
  1. Russell Petty
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  2. Alan Anthoney
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  3. Jean-Philippe Metges
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  4. Maria Alsina
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  5. Anthony Gonçalves
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  6. Jennifer Brown
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  7. Clara Montagut
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  8. Katharina Gunzer
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  9. Gianluca Laus
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  10. Jorge Luis Iglesias Dios
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  11. Bernardo Miguel-Lillo
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  12. Patrick Bohan
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  13. Ramón Salazar
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Corresponding author

Correspondence to Ramón Salazar.

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Conflict of interest

R. D. Petty has received funding from Roche and AstraZeneca, remuneration from Eli Lilly and Merck, and has had a consultant/advisory role for Eli Lilly and AstraZeneca. J. P. Metges has received remuneration from Amgen, Sanofi and Merck. P. Bohan is an employee of PharmaMar. J. L. Iglesias Dios is a shareholder and employee of PharmaMar. B. Miguel-Lillo and G. Laus are shareholders and former employees of PharmaMar. All other authors declare no conflicts of interest.

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Petty, R., Anthoney, A., Metges, JP. et al. Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial). Cancer Chemother Pharmacol 77, 819–827 (2016). https://doi.org/10.1007/s00280-016-2991-0

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  • DOI: https://doi.org/10.1007/s00280-016-2991-0

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