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Ref Type Journal Article
PMID (32741971)
Authors Martin-Liberal J, Hollebecque A, Aftimos P, Jungels C, Martin-Romano P, Rodon J, Kremer JD, Zhang W, Bendell J
Title First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours.
Journal Vol Issue Date Pages Journal Short Title
British journal of cancer 2020 Aug 03 1235-1243 Br J Cancer
URL
Abstract Text This is the first-in-human study of novel anti-angiopoietin-2 (Ang-2) monoclonal antibody LY3127804 as monotherapy and in combination with ramucirumab in advanced solid tumours.Patients received intravenous LY3127804 monotherapy (4, 8, 12, 16, 20 and 27 mg/kg) in part A; LY3127804 (8, 12, 16, 20 and 27 mg/kg) with 8 mg/kg ramucirumab in part B; and LY3127804 (20 mg/kg) with 12 mg/kg ramucirumab in part C. Treatments were administered every 2 weeks (Q2W) during 28-day cycles. Dose-escalation was based on cycle 1 dose-limiting toxicities (DLTs).Sixty-two patients were treated in part A (n = 20), part B (n = 35) and part C (n = 7). Constipation, diarrhoea and fatigue were the most common treatment-emergent adverse events (TEAEs) in part A; hypertension and peripheral oedema were the most frequent TEAE in parts B and C. No DLT was observed and maximum tolerated dose for LY3127804 was not reached. Four patients achieved partial response with combination therapy (clear cell endometrial carcinoma, cervix squamous cell carcinoma, carcinoma of unknown primary and gastroesophageal junction carcinoma), 29 achieved stable disease, and 24 had progressive disease.LY3127804 monotherapy and its combination with ramucirumab are well tolerated. LY3127804 20 mg/kg was the recommended Phase 2 dose.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
LY3127804 LY3127804 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
LY3127804 LY-3127804|LY 3127804|Zansecimab LY3127804 is an antibody that targets Angiopoietin-2 (Ang2), resulting in reduced angiogenesis, and potentially resulting in decreased tumor growth in combination with other agents (AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3259, PMID: 32741971).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References