Nxera Pharma and its partner Cancer Research UK have presented encouraging results from the completed phase 1 portion of their ongoing phase 1/2a clinical trial of HTL0039732, a novel oral EP4 antagonist, at the European Society for Medical Oncology Congress (ESMO) 2025 in Berlin.
The first-in-human trial is assessing HTL0039732 as a monotherapy and in combination with the checkpoint inhibitor atezolizumab in patients with advanced solid tumours resistant or refractory to standard treatments.
Cancer Research UK’s Centre for Drug Development is sponsoring and managing the trial. The lead site is Addenbrooke’s Hospital, Cambridge, with recruitment open across the Experimental Cancer Medicine Centre network.
The phase 1 study met its primary objectives, confirming safety and identifying a recommended phase 2 dose of 160mg QD in combination with atezolizumab. No grade 4 or 5 treatment-related adverse events were reported, and no dose-limiting toxicities were observed. Grade 3 treatment-related events occurred in 14% of patients receiving the combination, aligning with existing atezolizumab data.
Partial responses were confirmed in two patients: one with metastatic renal cell cancer and another with microsatellite stable colorectal cancer, a subgroup typically unresponsive to checkpoint inhibitors.
Dr Alastair Brown, SVP, Future Therapeutic Strategy at Nxera Pharma, said: “We are encouraged by the robust safety profile and promising results from the completed phase 1 study of our novel EP4 antagonist HTL0039732 in cancer patients whose tumors are resistant or refractory to standard therapy.”
He added: “Radiological responses in otherwise immunotherapy-resistant tumors demonstrate a potential to improve on current treatments and these data have enabled our partner CRUK to advance HTL’732 into the phase 2 expansion part of the trial in a more-defined group of solid tumors.”
The phase 2a trial is now underway, expanding into four patient cohorts.
