Browsing by Author "Funt, Samuel A."

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    A Phase II Study Assessing the Safety and Efficacy of ASP1650 in Male Patients with Relapsed Refractory Germ Cell Tumors
    (Springer, 2022) Adra, Nabil; Vaughn, David J.; Einhorn, Lawrence H.; Hanna, Nasser H.; Funt, Samuel A.; Rosales, Matt; Arozullah, Ahsan; Feldman, Darren R.; Medicine, School of Medicine
    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.
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    Phase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors
    (Springer, 2021) Ashkar, Ryan; Feldman, Darren R.; Adra, Nabil; Zaid, Mohammad Abu; Funt, Samuel A.; Althouse, Sandra K.; Perkins, Susan M.; Snow, Christin I.; Lazzara, Kayla M.; Sego, Lina M.; Quinn, David I.; Hanna, Nasser H.; Einhorn, Lawrence H.; Albany, Costantine; Biostatistics, School of Public Health
    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.