The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial.

Purpose: Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti-PD-1 inhibition.

Patients And Methods: This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design.

Tumour mutational burden as a biomarker in patients with mismatch repair deficient/microsatellite instability-high metastatic colorectal cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are the standard treatment in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Tumour mutational burden (TMB) is a promising biomarker for the prediction of treatment outcomes.

Patients And Methods: We screened 203 patients with dMMR/MSI-H mCRC treated with an anti-PD-(L)1 (anti-Programmed-Death-(Ligand)1) plus or minus an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA-4) agent at three Italian Academic Centers.