TPS626 Background: While most patients (pts) with metastatic GCTs are cured with first line cisplatin-based chemotherapy, 20-30% relapse after treatment. In pts that relapse, many are still cured with second or third-line chemotherapy. High-dose chemotherapy (HDCT) with peripheral blood stem-cell transplant (PBSCT) remains a standard in the salvage setting. Maintenance chemotherapy after salvage therapy has been evaluated to improve cure rates. In a retrospective series, oral etoposide after HDCT and PBSCT improved PFS compared to observation alone. A randomized prospective trial of daily oral etoposide for 3 months vs observation after HDCT is ongoing. Testicular cancer has also been shown to have a higher expression of VEGF than non-neoplastic testis and an overexpression of c-MET. Zanzalintinib is an oral TKI with multiple targets including MET, VEGFR2 and the TAM receptors (Tyro3, AXL and MER) with a shorter half-life, likely improving tolerability and allowing it to be combined with oral maintenance chemotherapy options. Based on this, we proposed a phase I/II trial investigating the use of the combination of zanzalintinib with oral etoposide as maintenance therapy for pts w/ relapsed GCTs post-HDCT with PBSCT, with a safety lead-in cohort. Methods: This is an open label, single arm phase I/II trial of maintenance zanzalintinib in combination with oral etoposide in pts with relapsed GCT treated with HDCT and PBSCT with a safety lead-in cohort in pts with relapsed, refractory metastatic GCT. In the safety lead-in cohort, eligible pts are adult men and women with GCT that have progressed after first-line cisplatin-based combination chemotherapy in addition to at least 1 salvage regimen and are considered incurable with standard therapies. Nine pts will initially be enrolled, and zanzalintinib will be administered at 40 mg daily in combination with daily oral etoposide at 50 mg daily. Bayesian Optimal Interval (BOIN) design will be used to determine the recommended phase II dose (RP2D) of zanzalinitib based on Dose Limiting Toxicities (DLT). The DLT window will be 28 days from cycle 1, day 1. After the safety lead-in, the primary endpoint will be 1-year PFS for pts treated with the combination after HDCT with PBSCT. In phase II, we plan to enroll 29 pts after HDCT with PBSCT within 16 weeks and treat with zanzalinitib at RP2D daily in combination with oral etoposide at 50 mg daily for 3 months. Secondary outcomes include 12-month OS and safety and tolerability of maintenance zanzalintinib in combination with oral etoposide. Exploratory evaluation of next generation sequencing (NGS) at time of enrollment will be performed and its correlation with PFS and OS will be evaluated as part of our exploratory objective. This study is currently enrolling patients. Clinical trial information: NCT06937866 .
Khalid et al. (Sun,) studied this question.