A phase 1/2a, multicenter, first-in-human, open-label clinical trial evaluating MDX2004 monotherapy in patients with advanced tumors.

Abstract

TPS2686 Background: MDX2004 is a trispecific antibody–fusion protein developed as an immunotherapy for advanced cancers. It is designed to stimulate T cells through engagement of CD3, CD28, and 4-1BB, thereby enhancing immune activation. MDX2004 is expected to promote activation and expansion of T lymphocytes, including stem and memory T-cell populations. Methods: This Phase 1/2, multicenter, first-in-human, open-label clinical trial evaluates MDX2004 in patients with advanced or metastatic solid tumors (NCT07110584). The study includes a Phase 1a dose-escalation stage guided by a Bayesian Optimal Interval (BOIN) design targeting a maximum tolerated dose toxicity rate of 30%; a Phase 1b indication-optimization stage in up to five tumor types; a Phase 1c dose-optimization stage in up to three indications; and a Phase 1d/2a expansion at the recommended Phase 2 dose (RP2D) in a single indication. In Phase 1a, patients with advanced solid tumors receive escalating intravenous doses of MDX2004. Phase 1b evaluates a selected dose in patients with homogeneous indications to assess preliminary efficacy. In Phase 1c, patients with selected indications are randomized 1:1 to two dose cohorts using a Bayesian Optimal Phase 2 (BOP2) design. Once the RP2D is established, Phase 1d/2a will enroll approximately 30 patients into a single cohort using a BOP2 design. The primary objectives across study phases are to characterize the safety, tolerability, and antitumor activity of MDX2004. Secondary endpoints include time to response, disease control rate, duration of response, pharmacokinetics, and immunogenicity. Radiologic tumor assessments are performed every 8 weeks, and treatment continues until disease progression per RECIST v1.1 (investigator assessed), unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. The study is planned to be conducted in Australia, Israel, Moldova; patient recruitment is ongoing. Clinical trial information: NCT07110584 .