Safety of unconventional antibody-drug conjugate L-DOS47 in a phase I/II monotherapy study targeting advanced NSCLC.

ABSTRACT:

Introduction

Tumor acidity is emerging as a hallmark of cancer and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression is frequently increased in acidic tumors. L-DOS47, a novel antibody-drug conjugate (ADC), consists of jack bean urease cross-linked to anti-CEACAM6 nanobodies. L-DOS47 is thus both targeted to CEACAM6-expressing tumors and designed to improve tumor control by neutralizing the acidic tumor microenvironment (TME) through ammonia and bicarbonate production from local urea.

Methods

This open-label, non-randomized study evaluated safety and tolerability of L-DOS47 in Stage IIIB/IV non-small cell lung cancer (NSCLC) patients. The Phase I 3 + 3 dose escalation aimed to determine the maximum tolerated dose (MTD) of L-DOS47 administered onc

SUBMITTER: Ramlau R 

PROVIDER: S-EPMC12375440 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature