Phase 1 study of ASP1002, a bispecific antibody targeting claudin 4 (CLDN4) and CD137, in patients with locally advanced (LA) or metastatic solid tumors that express CLDN4.

Abstract

TPS2670 Background: The lack of benefit for many cancers from newer-generation combination chemotherapies has stimulated research into targeted agents. CLDN4, a claudin protein family member that regulates tight junction formation, is highly expressed in multiple tumor types including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), colorectal cancer (CRC), prostate adenocarcinoma (PA), ovarian cancer (OC), and triple-negative breast cancer (TNBC). Following primary T cell activation, CD137 provides a costimulatory signal that enhances T cell proliferation and cytokine production. Together CLDN4 and CD137 represent promising therapeutic targets for solid tumors. ASP1002 is a bispecific antibody designed to target CLDN4 and CD137, thereby enhancing the antitumor response of T cells against CLDN4-expressing tumor cells. Methods: This phase 1 first-in-human, open-label, multicenter study (NCT05719558) is evaluating the safety and tolerability, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D) of ASP1002 in adult patients with LA or metastatic solid tumors that express CLDN4. The primary endpoint is safety and tolerability, as assessed by dose-limiting toxicities (DLTs), adverse events (AEs), serious AEs, laboratory tests, vital signs, ECGs, PEs, and ECOG performance status. Secondary endpoints are pharmacokinetic characteristics; confirmed objective response rate (ORR), duration of response, and disease control rate per iRECIST and RECIST 1.1; and incidence rate and expression levels of CLDN4 by immunohistochemistry. Dose escalation will include patients with LA or metastatic NSCLC, UC, CRC, PA, OC, or TNBC. ASP1002 will be administered at escalating doses Q1W IV on days 1, 8, 15 in a 21-day cycle until discontinuation to determine MTD and/or candidate RP2D regimens. At doses ≥10 mg, multi-participant cohorts will be included. Safety follow-up visits will occur within 7 days posttreatment, and on 30 and 90 days posttreatment. Next, dose expansion will enroll patients with LA or metastatic NSCLC, UC, CRC, and other tumor types with confirmed complete response (CR) or partial response (PR) in dose escalation. Candidate RP2D regimens based on dose escalation data will be evaluated in ≤40 patients per dose level, per tumor type in dose expansion. ORR (confirmed CR or PR) per iRECIST will be evaluated in tumor-specific expansion cohorts. The minimum number of responders needed to establish activity is 4 (NSCLC), 3 (CRC), and 7 (UC). Study enrollment is currently ongoing in the United States. Clinical trial information: NCT05719558 .