A Phase II Study Assessing the Safety and Efficacy of ASP1650 in Male Patients with Relapsed Refractory Germ Cell Tumors
dc.contributor.author | Adra, Nabil | |
dc.contributor.author | Vaughn, David J. | |
dc.contributor.author | Einhorn, Lawrence H. | |
dc.contributor.author | Hanna, Nasser H. | |
dc.contributor.author | Funt, Samuel A. | |
dc.contributor.author | Rosales, Matt | |
dc.contributor.author | Arozullah, Ahsan | |
dc.contributor.author | Feldman, Darren R. | |
dc.contributor.department | Medicine, School of Medicine | |
dc.date.accessioned | 2024-05-21T08:39:45Z | |
dc.date.available | 2024-05-21T08:39:45Z | |
dc.date.issued | 2022 | |
dc.description.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. | |
dc.eprint.version | Author's manuscript | |
dc.identifier.citation | Adra N, Vaughn DJ, Einhorn LH, 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. 2022;40(5):1087-1094. doi:10.1007/s10637-022-01276-w | |
dc.identifier.uri | https://hdl.handle.net/1805/40859 | |
dc.language.iso | en_US | |
dc.publisher | Springer | |
dc.relation.isversionof | 10.1007/s10637-022-01276-w | |
dc.relation.journal | Investigational New Drugs | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Testicular cancer | |
dc.subject | Germ cell tumor | |
dc.subject | ASP1650 | |
dc.title | A Phase II Study Assessing the Safety and Efficacy of ASP1650 in Male Patients with Relapsed Refractory Germ Cell Tumors | |
dc.type | Article |