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

• Published in: Investigational new drugs Vol. 40; no. 5; pp. 1087 - 1094
• Main Authors: Adra, Nabil, Vaughn, David J., Einhorn, Lawrence H., Hanna, Nasser H., Funt, Samuel A., Rosales, Matt, Arozullah, Ahsan, Feldman, Darren R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2022; Springer Nature B.V
• Subjects: Adult; Antibodies; Antibodies, Monoclonal - adverse effects; Anticancer properties; Antineoplastic Agents - adverse effects; Antitumor activity; Biomarkers; Chemotherapy; Effectiveness; Embryos; Epithelium; Histology; Humans; Immunoglobulin G; Immunohistochemistry; Male; Males; Medicine; Medicine & Public Health; Membranes; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasms, Germ Cell and Embryonal - drug therapy; Oncology; Patients; Pharmacology/Toxicology; Safety; Seminoma; Staining; Testicular cancer; Testicular Neoplasms - drug therapy; Therapeutic targets; Toxicity; Tumors; Young Adult; Germ cell tumor; Testicular cancer; ASP1650
• ISSN: 0167-6997; 1573-0646; 1573-0646
• DOI: 10.1007/s10637-022-01276-w

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/m 2 safety lead-in group, and 13 in 1500 mg/m 2 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/m 2 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).