Riether, Carsten; Pabst, Thomas; Höpner, Sabine; Bacher, Vera; Hinterbrandner, Magdalena; Banz, Yara; Müller, Rouven; Manz, Markus G.; Gharib, Walid H.; Ferreira, David; Bruggmann, Remy; Van Rompaey, Luc; Moshir, Mahan; Delahaye, Tim; Gandini, Domenica; Erzeel, Ellen; Hultberg, Anna; Fung, Samson; De Haard, Hans; Leupin, Nicolas; ... (2 December 2018). 2680 Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial (Unpublished). In: ASCO 2018. 2. Dezember 2018.
Outcomes in elderly patients with acute myeloid leukemia (AML) are still adverse, as the majority does not qualify for intensive therapy or allogenic stem cell transplantation (ASCT). DNA hypomethylating agents (HMAs) induce remissions and prolong survival in a fraction of these patients. However, overall prognosis remains dismal and all patients progress due to therapy-resistant leukemia stem cells (LSCs). We recently demonstrated that HMAs upregulate the expression of CD70 on primary human AML LSCs, potentially contributing to HMA resistance and that blocking the cell-autonomous CD70/CD27 signaling inhibits proliferation and myeloid differentiation of LSCs and contributes to HMA resistance. Consequently, combining HMA treatment with a blocking αCD70 monoclonal antibody potently reduced colony formation of AML LSCs in vitro and effectively eliminated human AML LCSs in xenograft experiments. Based on these results, we initiated an open-label, non-controlled, non-randomized Phase 1/2 trial combining the HMA azacitidine (AZA) with ARGX-110, a human monoclonal antibody targeting CD70, in newly diagnosed AML patients unfit for intensive chemotherapy (ARGX-110-1601, NCT03030612).
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