Open AccessPhase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors
Author(s) -
Ryan Ashkar,
Darren R. Feldman,
Nabil Adra,
Mohammad Abu Zaid,
Samuel A. Funt,
Sandra K. Althouse,
Susan M. Perkins,
Carlton J. Snow,
Kayla Marie Lazzara,
Lina M. Sego,
David I. Quinn,
Nasser H. Hanna,
Lawrence H. Einhorn,
Costantine Albany
Publication year - 2021
Publication title -
investigational new drugs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 87
eISSN - 1573-0646
pISSN - 0167-6997
DOI - 10.1007/s10637-021-01134-1
Subject(s) - brentuximab vedotin , medicine , chemotherapy , germ cell tumors , chemotherapy regimen , regimen , cd30 , oncology , gastroenterology , antibody drug conjugate , surgery , immunology , immunohistochemistry , antibody , monoclonal antibody
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.