A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific antibody in subjects with germ cell tumors and other advanced solid tumors.

TPS652 Background: Claudin-6 (CLDN6) is overexpressed in solid tumors including germ cell tumors (GCTs) with minimal expression in healthy tissue. This differential expression profile makes CLDN6 a suitable tumor-associated antigen for a T-cell engaging bispecific antibody (bsAb). XmAb541 is a first-in-class humanized, anti-CLDN6 x anti-CD3 bsAb that directs T-cell cytotoxicity. The XmAb 2+1 format provides avid tumor targeting and selectivity. Importantly, XmAb541 selectively binds CLDN6, with reduced binding to other claudin family proteins (e.g., CLDN9) and non-CLDN6-expressing healthy tissue [1]. This study focuses on subjects with GCT and other CLDN6+ solid tumors who have failed standard therapy and have a high unmet medical need. The primary objective of the trial is to determine an optimal and tolerated dose(s) for further evaluation. Methods: This is a first-in-human, Phase 1, open-label study to evaluate the safety and tolerability of XmAb541 in advanced solid tumors. The study will be conducted in 2 Parts. Part 1, Dose Escalation, will establish a dosing regimen inclusive of a priming dose, step-up dose(s), and the target dose. Part 2 Dose Expansion will further evaluate safety and tolerability and provide an initial evaluation of preliminary antitumor activity for the dose regimen(s) established in Part 1. XmAb541 will be administered intravenously. Key inclusion criteria are age ≥ 18 years (for subjects with GCTs, age ≥15 years). Have histological evidence of locally advanced, recurrent, or metastatic GCT, ovarian, fallopian tube, peritoneal cancer, or adenocarcinoma of the endometrium. Have documented progressive disease on standard-of-care therapies; exhausted therapies with a survival benefit, or the standard therapy has no survival benefit or proven to be ineffective, intolerable, or subject is not a candidate for such available therapy. Subjects must have an Eastern Cooperative Oncology Group performance status of 0-2 and a life expectancy ≥ 3 months with adequate liver, kidney, and bone marrow function. Key exclusion criteria include the following: known active central nervous system metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate, provided they are radiologically stable. Ethics approval: This study was approved by WCG IRB. References: 1. Faber, M. Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells. (AACR 2021, Abstract No. 1860). Clinical trial information: NCT06276491 .