A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors Journal Article
| Authors: | Adra, N.; Vaughn, D. J.; Einhorn, L. H.; Hanna, N. H.; Funt, S. A.; Rosales, M.; Arozullah, A.; Feldman, D. R. |
| Article Title: | A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors |
| 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). |
| Journal Title: | Investigational New Drugs |
| Volume: | 40 |
| Issue: | 5 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2022-10-01 |
| Start Page: | 1087 |
| End Page: | 1094 |
| Language: | English |
| DOI: | 10.1007/s10637-022-01276-w |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PUBMED: | 35759134 |
| PMCID: | PMC10207925 |
| DOI/URL: | |
| Notes: | Accession Number: 158654337 -- Entry Date: In Process -- Revision Date: 20220824 -- Publication Type: Article -- Journal Subset: Biomedical; USA -- NLM UID: 8309330. -- Source: Cinahl |
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