Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS)

Non-melanoma skin cancer (NMSC) is the most common post-transplant malignancy in solid organ transplant (SOT) recipients and occurs at a 7–53x higher incidence vs. the general population. Additionally, the optimal management of NMSC in SOT is not well established. RP1 is an oncolytic immunotherapy (HSV-1) that expresses GM-CSF and a fusogenic glycoprotein (GALV-GP-R−). 

During an oral presentation at the AACR 2024 Annual Meeting, interim findings from the ARTACUS trial of RP1 monotherapy in solid organ and hematopoietic cell transplant recipients with skin cancers were unveiled. As of the data, cutoff date on September 18, 2023, RP1 monotherapy, administered for up to 25 doses, demonstrated a significant ORR of 34.8% among the evaluated patients. This included 5 complete responses and 3 partial responses, with the majority of responses still ongoing at the time of the data cutoff. Among the evaluated cohort (n=23), 20 had cutaneous squamous cell carcinoma (CSCC) and three had merkel cell carcinoma. Notably, a patient treated with RP1 for CSCC also experienced a complete response of a newly emerged primary basal cell carcinoma post baseline. 

The treatment demonstrated no signs of allograft rejection, including hepatic and lung allografts, and was well tolerated, maintaining a safety profile akin to non-immunocompromised patients with advanced skin cancers. The most common TEAEs were fatigue (33.3%), chills (25.9%), and pyrexia (25.9%). Further biomarker analysis revealed a rise in CD8+ T cells, a subset of immune cells, along with an elevation in PD-L1 expression following treatment, indicating immune activation. These initial results underscore the potential efficacy of RP1 monotherapy in treating skin cancers among transplant recipients, highlighting its promising role in this patient population.

KOL insights

“Organ transplant recipients are at a higher risk for skin cancer when compared to the broader population and have access to a limited number of treatment options given that systemic immunotherapy is typically contra-indicated.”–Expert Opinion.

Conclusion

In this groundbreaking clinical trial, intratumoral RP1 monotherapy was evaluated in solid organ transplant patients receiving chronic immunosuppressive therapy for advanced skin cancer, a population typically ineligible for systemic immunotherapy. More importantly, no instances of allograft rejection were observed, even in hepatic and lung transplant recipients. RP1 monotherapy exhibited favorable tolerability, aligning with safety profiles observed in non-immunocompromised patients with advanced skin cancers, as evidenced by the IGNYTE study. Lastly, these findings suggest that RP1 monotherapy holds promise as a viable treatment option for solid organ transplant patients with advanced skin cancer, offering potential therapeutic benefits without compromising safety.