Figure 3.

Potential role for an ATR inhibitor (ATRi) to overcome immune checkpoint inhibitor (ICI)-refractory Merkel cell carcinoma (MCC) and a clinical trial concept. (A) Prospective mechanism of action for an enhanced immune response in MCC treated with an ATRi ± radiotherapy (RT). (B) Schematic for a potential clinical trial of an ATRi for patients with MCC refractory to ICIs wherein an ATRi would be added to a patient’s ongoing PD-1 pathway blockade. Palliative RT may be utilized to control progressive lesions and potentially synergize with the ATRi. Abbreviations: cGAMP: cyclic guanosine monophosphate–adenosine monophosphate, α-PD-(L)1: anti-PD-(L)1, PFS: progression-free survival, RECIST: response evaluation criteria in solid tumors, SD: stable disease.