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A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors

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Abstract

Claudin6(CLDN6) is a tight junction protein of claudin-tetraspanin family and is of the earliest molecules expressed in embryonic epithelium. CLDN6 is frequently aberrantly expressed in testicular germ-cell tumors(GCT). ASP1650 is a chimeric-mouse/human-IgG1 antibody directed against CLDN6. Two-part, open-label, phase-II trial investigating ASP1650 in patients with relapsed/refractory GCT and no curable options. Part1 was a safety lead-in to establish the recommended-phase-II-dose(RP2D). Part2 was a phase-II study designed to evaluate the antitumor effects of ASP1650. CLDN6 expression was centrally assessed on archival tumor tissue using immunohistochemistry. The primary objectives were to establish the RP2D(safety lead-in) and the antitumor activity(phase-II) of ASP1650. Nineteen male patients were enrolled: 6 patients in 1000 mg/m2 safety lead-in group, and 13 in 1500 mg/m2 group. Median age 37.2 years(range,20–58). Histology was non-seminoma in 17/19 patients. Median number of previous chemotherapy regimens was 3. Thirteen patients had prior high-dose chemotherapy. No dose-limiting toxicity events were reported at any study drug dose. A RP2D of 1500 mg/m2 every 2 weeks was established. No partial or complete responses were observed. The study was stopped at the end of Simon Stage-I due to lack of efficacy. 15/16 subjects with available tissue had CLDN6 positive staining. The mean percent membrane staining was 71.6% and the mean membrane H score was 152.6(SD 76). ASP1650 did not appear to have clinically meaningful single-agent activity in relapsed/refractory GCT. CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081).

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If further data is requested, please contact Nabil Adra, MD (nadra@iu.edu).

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Acknowledgements

The authors thank all patients and their families, investigators, and research teams who participated in this study. This study was funded by Astellas.

Funding

This study was funded by Astellas.

Author information

Authors and Affiliations

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

    Nabil Adra, Lawrence H. Einhorn & Nasser H. Hanna

  2. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    David J. Vaughn

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

    Samuel A. Funt & Darren R. Feldman

  4. Weill Cornell Medical College, New York, NY, USA

    Samuel A. Funt & Darren R. Feldman

  5. Astellas Pharma US, Inc, Northbrook, IL, USA

    Matt Rosales & Ahsan Arozullah

Authors
  1. Nabil Adra
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  2. David J. Vaughn
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  3. Lawrence H. Einhorn
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  4. Nasser H. Hanna
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  5. Samuel A. Funt
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  6. Matt Rosales
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  7. Ahsan Arozullah
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  8. Darren R. Feldman
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Contributions

Study design: Adra, Vaughn, Einhorn, Rosales, Arozullah, Feldman, Acquisition of study data: Adra, Vaughn, Einhorn, Hanna, Funt, Feldman Analysis of study data: Adra, Vaughn, Rosales, Arozullah, Funt, Feldman Interpretation of study data: all authors Draft and approve final manuscript: all authors.

Corresponding author

Correspondence to Nabil Adra.

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Ethics approval and consent to participate

The study was approved by the institutional review board (IRB) of each participating institution (Indiana University, University of Pennsylvania, Memorial Sloan Kettering).

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Will be disclosed online. The authors declare no competing interests.

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Adra, N., Vaughn, D.J., Einhorn, L.H. et al. A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors. Invest New Drugs 40, 1087–1094 (2022). https://doi.org/10.1007/s10637-022-01276-w

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  • DOI: https://doi.org/10.1007/s10637-022-01276-w

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