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Investigational New Drugs

, Volume 37, Issue 4, pp 748–754 | Cite as

Phase II study of avelumab in multiple relapsed/refractory germ cell cancer

  • M. MegoEmail author
  • D. Svetlovska
  • M. Chovanec
  • M. Rečkova
  • K. Rejlekova
  • J. Obertova
  • P. Palacka
  • Z. Sycova-Mila
  • U. De Giorgi
  • J. Mardiak
PHASE II STUDIES
  • 35 Downloads

Summary

Background Germ cell tumors (GCTs) are highly curable diseases; however, not all patients can be cured. Patients in their second relapse have especially poor prognoses. PD-L1 expression is significantly higher in GCTs than in normal testicular tissue, and high PD-L1 expression is associated with a poor prognosis. This study aimed to determine the efficacy and safety of avelumab, a PD-L1 inhibitor, in patients with GCTs. Methods In this phase 2 study, patients with multiple relapsed and/or refractory GCTs were treated with avelumab at a dose of 10 mg/kg administered biweekly until progression or unacceptable toxicity. The primary endpoint was 12-week progression-free survival (PFS). Fifteen evaluable patients had to be enrolled in the first cohort, and if <8 of 15 patients had 12-week PFS, the study was to be terminated. Here, we report the results of the first stage of the trial. Results From November 2017 to January 2018, 8 patients with a median age of 29 years (range, 22 to 52 months) were enrolled. Patients were pretreated with a median of 5 (range, 1 to 6) previous lines of platinum-based therapies; 5 tumors (62.5%) were absolutely refractory to cisplatin, and 5 patients (62.5%) had visceral nonpulmonary metastases. At a median follow-up period of 2.6 months (range, 0.3 to 14.4), all the patients experienced disease progression, and 7 patients (87.5%) died. The twelve-week PFS was 0%, median PFS was 0.9 months (95% CI 0.5–1.9), and median OS was 2.7 months (95% CI 1.0–3.3). Avelumab was well tolerated, and no severe adverse events were observed. Conclusions This study failed to achieve its primary endpoint. Our data suggest a lack of avelumab efficacy in unselected multiple relapsed/refractory GCTs.

Keywords

Avelumab Germ cell tumors Immune checkpoint inhibitors PD-L1 expression Refractory germ cell tumors 

Notes

Acknowledgments

We would like to acknowledge Dr. De Angelis V, Dr. Miskovska V and Dr. Andrasina I for their collaboration and Krieschova A, Jancikova A, Turnova S, Gombarova V, Polakova H and Pekova Z for providing administrative support.

Author contributions

M-M, MC-C, U-DG and J-M participated in the conception and design of this study. D-S and M-R participated in data validation, and K-R, J-O, P-P, and Z-SM acquired, analyzed and interpreted the data. M-M drafted the article, and all the authors reviewed it critically for its important intellectual content.

Funding

This work was supported by the Scientific Grant Agency of the Ministry of Education (Projects No. VEGA 1/0174/19 and VEGA 1/0043/18).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All the procedures performed in studies involving human participants were conducted 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.

Informed consent

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M. Mego
    • 1
    • 2
    • 3
    Email author
  • D. Svetlovska
    • 1
    • 3
  • M. Chovanec
    • 2
    • 3
  • M. Rečkova
    • 3
  • K. Rejlekova
    • 2
    • 3
  • J. Obertova
    • 2
    • 3
  • P. Palacka
    • 2
    • 3
  • Z. Sycova-Mila
    • 3
  • U. De Giorgi
    • 4
  • J. Mardiak
    • 2
    • 3
  1. 1.Translational Research Unit, Faculty of Medicine, National Cancer InstituteComenius UniversityBratislavaSlovakia
  2. 2.2nd Department of Oncology, Faculty of MedicineComenius University and National Cancer InstituteBratislavaSlovak Republic
  3. 3.National Cancer InstituteBratislavaSlovak Republic
  4. 4.Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS - Medical Oncology Department MeldolaMeldolaItaly

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