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

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Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial (Unpublished).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).

Item Type:

Conference or Workshop Item (Poster)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Riether, Carsten; Pabst Müller, Thomas Niklaus; Höpner, Sabine; Bacher, Vera Ulrike; Hinterbrandner, Magdalena; Banz Wälti, Yara; Ferreira Francisco, David Miguel; Bruggmann, Rémy and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

23 Dec 2019 14:37

Last Modified:

23 Dec 2019 14:37

URI:

https://boris.unibe.ch/id/eprint/131613

Actions (login required)

Edit item Edit item
Provide Feedback