XMT-1660: A phase I, first-in-human trial of a B7-H4-directed dolasynthen antibody-drug conjugate in ovarian, endometrial, and breast cancers
Recommended Citation
Burger R, Hamilton E, Adams S, Han H, Spira A, Giordano A, Chaudhry A, Parajuli R, Wang J, Weise A, Abuhadra N, McNamara P, Kalinsky K. XMT-1660: A phase I, first-in-human trial of a B7-H4-directed dolasynthen antibody-drug conjugate in ovarian, endometrial, and breast cancers. Gynecol Oncol 2024; 190:S282.
Document Type
Conference Proceeding
Publication Date
11-1-2024
Publication Title
Gynecol Oncol
Abstract
Objectives: Ovarian (OC), endometrial (EC), and breast cancers (BC) are some of the leading causes of cancer death among women. Despite therapeutic advances, many patients develop resistance to available standard of care (SOC) therapies. B7-H4 is a poor prognostic factor and is overexpressed in several cancers, including OC, EC, and BC, with limited expression in normal healthy tissue. As a cell surface protein, member of the CD28/B7 immune checkpoint family, B7-H4 promotes tumorigenesis by suppressing antitumor immunity. XMT-1660 is a B7-H4-directed dolasynthen antibody-drug conjugate (ADC) designed with a precise, optimized drug-to-antibody ratio (DAR 6) and a proprietary microtubule inhibitor payload with controlled bystander effect. In the pre-clinical setting, XMT-1660 has demonstrated antitumor activity in OC, EC, and BC PDX models. The FDA has granted fast track designation to XMT-1660 for the treatment of adult patients with advanced or metastatic triple-negative breast cancer. Methods: The phase I trial includes a first-in-human dose escalation (DES) evaluating XMT-1660 among patients with solid tumors, including OC, EC, and BC, following progression on SOC. In the DES, a BOIN design will be used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). The DES and backfill cohorts will assess safety and preliminary efficacy. Patients are not selected by B7-H4 status, but baseline tumor samples are collected for retrospective analysis. The primary endpoints in the expansion portion (EXP) are safety and tolerability, overall response rate, disease control rate, and duration of response. The trial is currently enrolling patients. NCT05377996
Volume
190
First Page
S282
