A Phase 1b study evaluated the immunotherapy simlukafusp alfa in patients with metastatic renal cell carcinoma. The drug was tested in combination with atezolizumab, with or without bevacizumab. While the treatment showed biological activity, it did not improve outcomes compared to current standard therapies.
The triplet combination showed higher response rates than the doublet. The objective response rate was 25% with the doublet and 47.4% with the triplet. Disease control rates were 60.7% and 89.5%, respectively. Median progression-free survival was 6.3 months for the doublet and 18.3 months for the triplet, although no formal statistical comparison was made.
Side effects were common but manageable. All patients experienced treatment-related adverse events, including fever, chills, and nausea. Liver abnormalities and infusion reactions were also frequent. Serious side effects occurred in 58% of patients, including two treatment-related deaths.
Despite limited clinical benefit, the drug successfully activated the immune system. It increased natural killer cells and CD8+ T cells and enhanced immune cell infiltration into tumors. Although development in this setting is unlikely to continue, the findings support further research into next-generation IL-2–based therapies.