A phase I trial evaluated cemiplimab, a PD-1 inhibitor, in 12 kidney transplant recipients (KTRs) with advanced cutaneous squamous cell carcinoma (CSCC). Patients were cross-tapered from immunosuppressive therapy to an mTOR inhibitor and pulsed corticosteroids before receiving cemiplimab. No kidney rejection events were observed, and five of 11 evaluable patients (46%) showed a response, including two with durable responses. The median follow-up was 6.8 months, with a median duration of response of 11.4 months. Treatment-related adverse events occurred in 42% of patients, including diarrhea, infection, and metabolic disturbances. One patient died due to angioedema and anaphylaxis. The combination of mTOR inhibitor and corticosteroids provided a favorable immunosuppressive regimen, allowing for durable antitumor responses without kidney rejection. The study highlights the potential of PD-1 inhibitors in KTRs with CSCC, despite the risk of allograft rejection. The results suggest that this regimen may be a viable option for future trials in this population. The study was funded by Regeneron Pharmaceuticals.A phase I trial evaluated cemiplimab, a PD-1 inhibitor, in 12 kidney transplant recipients (KTRs) with advanced cutaneous squamous cell carcinoma (CSCC). Patients were cross-tapered from immunosuppressive therapy to an mTOR inhibitor and pulsed corticosteroids before receiving cemiplimab. No kidney rejection events were observed, and five of 11 evaluable patients (46%) showed a response, including two with durable responses. The median follow-up was 6.8 months, with a median duration of response of 11.4 months. Treatment-related adverse events occurred in 42% of patients, including diarrhea, infection, and metabolic disturbances. One patient died due to angioedema and anaphylaxis. The combination of mTOR inhibitor and corticosteroids provided a favorable immunosuppressive regimen, allowing for durable antitumor responses without kidney rejection. The study highlights the potential of PD-1 inhibitors in KTRs with CSCC, despite the risk of allograft rejection. The results suggest that this regimen may be a viable option for future trials in this population. The study was funded by Regeneron Pharmaceuticals.