Nxera Pharma and Cancer Research UK are set to present findings from their ongoing Phase 1/2a clinical trial of HTL0039732, an innovative cancer immunotherapy drug, at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain. The presentation will highlight the drug's potential in treating a range of advanced solid tumors.
HTL0039732, also known as NXE0039732, is an orally administered EP4 antagonist. It is designed to be used in combination with other immunotherapies to treat a wide range of cancers. The trial is sponsored and managed by Cancer Research UK’s Centre for Drug Development.
Mechanism of Action
HTL0039732 functions by selectively blocking signaling through the prostaglandin E2 (PGE2)-type prostanoid receptor 4 (EP4). PGE2, present in the tumor microenvironment, enables cancer cells to evade immune detection. By inhibiting EP4, HTL0039732 enhances the immune system's capacity to recognize and control cancer cells. This mechanism makes it a promising candidate for cancers that typically show poor response to existing immunotherapies.
Trial Design and Objectives
The Phase 1/2a trial (NCT05944237) is a first-in-human study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of HTL0039732. The drug is being assessed both as a monotherapy and in combination with the checkpoint inhibitor atezolizumab in patients with advanced solid tumors. The trial's co-chief investigators are Dr. Bristi Basu from the University of Cambridge, and Dr. Debashis Sarker from Guy’s and St Thomas’ NHS Foundation Trust, who will present a “Trial in Progress” poster at ESMO 2024.
Clinical Progress and Enrollment
The first patient was dosed in August 2023, and the trial is actively recruiting participants at Addenbrooke’s Hospital in Cambridge, Guy’s Hospital in London, and the Christie Hospital in Manchester. Dr. Sarker emphasized the importance of targeting EP4 within the tumor immune microenvironment, expressing hope that the trial will uncover a novel approach to enhance the immune system and improve treatment outcomes for patients with various solid cancers.
Nxera’s NxWave Platform
HTL0039732 was rationally designed using Nxera’s NxWave™ platform and has undergone extensive translational and preclinical evaluations. The upcoming presentation at ESMO will provide further insights into the trial's progress and future directions.
