Nxera Pharma and Cancer Research UK have announced the first patient has been dosed in a phase 2a trial of HTL0039732, an investigational oral EP4 antagonist being developed to treat advanced solid tumours in combination with immunotherapy.
The trial follows successful completion of phase 1, which identified a safe and well-tolerated dose of HTL0039732 with checkpoint inhibitor atezolizumab. The drug showed good target engagement of EP4 without significantly affecting EP2.
Early efficacy signals included two confirmed partial responses in distinct tumour types. Full phase 1 results will be presented at the European Society for Medical Oncology Congress in October.
HTL0039732 blocks signalling through the prostaglandin E2 receptor EP4, which helps cancer cells evade immune detection. By inhibiting EP4, the drug may enhance immune response against tumours that typically resist current immunotherapies.
The trial is sponsored and managed by Cancer Research UK’s Centre for Drug Development. It is led by Chief Investigator Dr Bristi Basu, University of Cambridge, and Co-Chief Investigator Dr Debashis Sarker, King’s College London. Recruitment is underway across the Experimental Cancer Medicine Centre network.
The phase 2a study includes four patient cohorts: microsatellite stable colorectal cancer, gastric or gastroesophageal junction adenocarcinoma, clear cell renal cell carcinoma, and metastatic castration-resistant prostate cancer.
Dr Matt Barnes, Chief Scientific Officer and President of Nxera Pharma UK, said: “We are proud to reach this important milestone in the development of HTL0039732 and to continue our productive collaboration with Cancer Research UK.”
Dr Bristi Basu said: “It is exciting to move to the next phase of assessing this new inhibitor of an important receptor EP4, which is implicated in suppression of the antitumor immune response.”
Dr Lars Erwig added: “The dosing of the first patient in the phase 2a trial of HTL0039732 is a significant step forward.”
