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

Abstract

TPS424 Background: Testicular cancer (TC) is the most common solid malignancy in men aged 15-35 yrs; germ cell tumors (GCTs) account for 95% of TC. Claudin 6 (CLDN6) is a tight junction membrane protein whose expression in normal tissue is confined to embryonic cells but is frequently aberrantly expressed in GCTs. ASP1650 (also known as IMAB027) is a monoclonal antibody targeted against CLDN6 that can induce antibody-dependent cell-mediated and complement-dependent cytotoxicity in CLDN6-expressing cells and has demonstrated potent antitumor effects in preclinical models of TC. Methods: This phase 2 study with a safety run-in (NCT03760081) will enroll ≤46 male patients (pts) with advanced GCTs who have had prior cisplatin-based combination chemotherapy and ≥1 salvage regimen. In the safety run-in, an initial ASP1650 dose level will be evaluated in 3 pts. If tolerated, a new cohort of 3 pts will begin at the next dose level per the Bayesian Optimal Interval Design. A Dose Evaluation Committee will assess tolerability and determine maximum tolerated dose. Once the recommended phase 2 dose (RP2D) has been established, ≤34 pts will be enrolled in phase 2 and will receive ASP1650 in 2-week cycles for up to 12 cycles or until study discontinuation criteria is met. Phase 2 of the study will utilize a Simon’s 2-stage design to allow for early termination. In stage I, 13 pts, including pts from the RP2D cohort of the safety run-in, will be evaluated for response. If there is ≤1 response among these 13 pts, the study will be stopped, otherwise an additional 21 pts will be enrolled in stage II. Primary endpoints of the study include establishment of the RP2D and confirmation of overall response rate, as assessed by modified RECIST v1.1 response criteria (RECIST v1.1 + serum tumor markers [βhCG and AFP]). Secondary endpoints include the determination of safety/tolerability and pharmacokinetic profiles as well as other efficacy measures (eg, clinical benefit rate; progression-free survival; change in serum tumor biomarkers). Enrollment is currently ongoing; as of Sept 12, 2019, 6 pts have enrolled and 2 are still on active treatment. Clinical trial information: NCT03760081.