EP4 receptor antagonist for immuno-oncology
Immunotherapy has dramatically changed oncology therapy from palliative care to curative treatment. However, immunotherapy does not work for about 50% of patients with responsive cancers, and many solid tumours are not responsive at all.
Recent nonclinical and clinical studies have demonstrated that combination therapies of immune checkpoint inhibitors (ICIs) and other immunomodulators can significantly enhance the patient’s response. This is the reason why immuno-oncology has emerged as an important application for the targeted immunomodulator CR6086. EP4 signalling plays a major immunosuppressive role in the tumour microenvironment, and as such it favours cancer immune escape and tumour progression. Experimental evidence suggests that CR6086, as well as other EP4 receptor antagonists, may improve the response of tumours to immuno-oncology therapies, e.g. immune checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 drugs.
Compared with other EP4 antagonists entering studies in immuno-oncology, CR6086 has already a large clinical database for other indications. On top of this, the pharmacokinetics and pharmacodynamics of CR6086 suggest that it may be the current best-in-class EP4 receptor antagonist.
An important application is the combination of CR6086 with immune checkpoint inhibitors in patients who have advanced cancer and/or inadequate response to anti-PD-1/PD-L1 therapy in selected indications (e.g. proficient mismatch repair – microsatellite stable – colorectal cancer where ICIs are not effective). A Phase I/II clinical trial to evaluate the safety and efficacy of CR6086 in combination with the PD-1 inhibitor balstilimab (Agenus, Inc.) in patients with pretreated mismatch-repair-proficient and microsatellite stable metastatic colorectal cancer is ongoing (NCT05205330).
Rottapharm Biotech is looking for a partnership to progress CR6086 development in immuno-oncology.