Background: High-dose IL-2 is approved for patients with metastatic melanoma and renal cell carcinoma but is associated with significant toxicity, frequently requiring intensive care. RO6874281 carries an engineered IL2v moiety with abolished binding to IL-2Ra. Affinity to IL-2Rβγ is retained, resulting in activation of immune effector CD8 T and NK lymphocytes, but reduced activity on regulatory T cells (Tregs). The antibody part of RO6874281 binds with high affinity to FAP, which is strongly expressed on tumor-associated fibroblasts, and mediates retention and accumulation in malignant lesions.