A phase 1 study of durvalumab as monotherapy or combined with tremelimumab with or without azacitidine in patients with myelodysplastic syndrome.

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status). Primary safety endpoints included dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). Secondary endpoints included evaluation of clinical outcomes, survival, and pharmacokinetics. Dose-limiting toxicities were experienced by no patients in part 1 and 3 patients (11%) in part 2. The most common treatment-emergent adverse events were diarrhea and fatigue (40% each) in part 1 and fatigue (44%) and anemia (37%) in part 2. In parts 1 and 2, 15% of patients experienced marrow complete response as their best overall response, according to IWG criteria. Hematologic improvement was observed in 35% and 30% of patients respectively in part 1 and part 2. The study was terminated early due to limited efficacy.