XMT-1660: A Phase 1b trial of a B7-H4 targeting antibody drug conjugate (ADC) in endometrial, ovarian, and breast cancers (1250)

Document Type

Conference Proceeding

Publication Date

9-1-2023

Publication Title

Gynecol Oncol

Abstract

Objectives: Endometrial (EC) and ovarian cancers (OC) are some of the leading causes of cancer death among women. Despite therapeutic advances, many patients eventually develop resistance to available standard-of-care (SOC) therapies. B7-H4 is a poor prognostic factor and is overexpressed in several cancers, including endometrial, ovarian, and breast. As a member of the CD28/B7 family of cell surface proteins, it promotes tumorigenesis by suppressing antitumor immunity. XMT-1660 is a B7-H4-targeted Dolasynthen antibody drug conjugate (ADC) designed with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with a controlled bystander effect. In the preclinical setting, XMT-1660 has demonstrated antitumor activity in EC and OC PDX models. Methods: The phase I trial includes a first-in-human dose escalation (DES) portion followed by a dose expansion (EXP) evaluating XMT-1660 in patients with endometrial, ovarian, and breast cancers following progression on SOC. In the DES, BOIN (Bayesian Optimal Interval) design will be used to determine the MTD. The DES will assess the safety and preliminary efficacy and establish recommended phase II dose (RP2D). In the EXP portion, cohorts enrolling EC/OC, TNBC, ER+/HER2- BC are planned, and additional patients may be enrolled based on emerging data. The primary endpoints are safety and tolerability, overall response rate, disease control rate, and duration of response. Patients are not selected by B7-H4 status, but baseline tumor samples are collected for retrospective analysis. The trial is currently enrolling patients.

Medical Subject Headings

Hematology

PubMed ID

Not assigned.

Volume

176

First Page

S158

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