Details

Autor(en) / Beteiligte

• Sikic, Branimir I
• Lakhani, Nehal
• Patnaik, Amita
• Shah, Sumit A
• Chandana, Sreenivasa R
• Rasco, Drew
• Colevas, A Dimitrios
• O'Rourke, Timothy
• Narayanan, Sujata
• Papadopoulos, Kyriakos
• Fisher, George A
• Villalobos, Victor
• Prohaska, Susan S
• Howard, Maureen
• Beeram, Muralidhar
• Chao, Mark P
• Agoram, Balaji
• Chen, James Y
• Huang, Jie
• Axt, Matthew
• Liu, Jie
• Volkmer, Jens-Peter
• Majeti, Ravindra
• Weissman, Irving L
• Takimoto, Chris H
• Supan, Dana
• Wakelee, Heather A
• Aoki, Rhonda
• Pegram, Mark D
• Padda, Sukhmani K

Titel

First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers

Ist Teil von

• Journal of clinical oncology, 2019-04, Vol.37 (12), p.946-953

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis. Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort. Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months. 5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.