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Phase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors

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Summary

Background CD-30 is highly expressed in some patients with non-seminomatous germ-cell tumors. Brentuximab vedotin is an antibody–drug conjugate directed to CD-30. We report a phase 2 trial of brentuximab vedotin in patients with chemo-refractory GCT. Patients and methods This is a single arm, two cohort phase 2 trial investigating brentuximab vedotin 1.8 mg/kg IV every 3 weeks until disease progression or intolerable toxicities in patients with relapsed GCT who have no curative options. Patients with mGCT who progressed after first line cisplatin-based chemotherapy and after at least 1 salvage regimen (high-dose or standard-dose chemotherapy) were eligible. CD30 expression was assessed and two cohorts defined: CD30 positive and CD30 negative/unknown. Results 18 patients were enrolled. Median age 34.7 (range, 23–56). All patients had non-seminoma. Median AFP 4.9 (range, 1–219,345) and hCG 282 (range, 0.6–172,064). Five patients had late relapse (> 2 years). Median number of previous chemotherapy regimens was 3 (range, 2–7). Ten patients received prior high-dose chemotherapy. Seven patients had positive CD30 staining. There were two grade 3 treatment-related adverse events. No partial or complete responses were observed. 6 patients achieved radiographic stable disease (range, 9–14.9 weeks), 5 had elevated AFP or hCG at trial entry and all 5 had transient > 50% decline in baseline AFP/hCG: 4 had CD30 -ve and 2 had CD30 + ve staining; 10 patients had progression of disease as their best response; 2 were not evaluable for response. Conclusion Brentuximab vedotin does not appear to have clinically meaningful single-agent activity in patients with refractory GCT.

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Funding

This work was supported by Seattle Genetics. No grant number is applicable.

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Author notes

  1. Ryan Ashkar and DarrenR. Feldman contributed equally to this article.

Authors and Affiliations

  1. Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, USA

    Ryan Ashkar, Nabil Adra, Mohammad Abu Zaid, Christin I. Snow, Kayla M. Lazzara, Lina M. Sego, Nasser H. Hanna, Lawrence H. Einhorn & Costantine Albany

  2. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Darren R. Feldman & Samuel A. Funt

  3. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA

    Sandra K. Althouse & Susan M. Perkins

  4. University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA

    David I. Quinn

Authors
  1. Ryan Ashkar
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  2. Darren R. Feldman
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  3. Nabil Adra
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  4. Mohammad Abu Zaid
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  12. Nasser H. Hanna
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  13. Lawrence H. Einhorn
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  14. Costantine Albany
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Contributions

Study concept and design: Adra, Feldman, Einhorn, Albany. Financial and administrative support: Adra. Provision of study materials or patients: Adra. Collection and assembly of data: All authors. Data analysis and interpretation: All authors. Drafting and writing: Ashkar, Adra. Review and final approval of manuscript: All authors.

Corresponding author

Correspondence to Nabil Adra.

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This study was approved by the Indiana University IRB.

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Informed consent was obtained from all individual participants in this study.

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Key Message

In this phase II trial, brentuximab vedotin was well tolerated but did not appear to have single agent activity in refractory germ cell tumors. CD-30 staining was positive in 7 patients. Six patients had stable disease while the rest had progressive disease as best response.

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Ashkar, R., Feldman, D.R., Adra, N. et al. Phase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors. Invest New Drugs 39, 1656–1663 (2021). https://doi.org/10.1007/s10637-021-01134-1

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