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|Ref Type||Journal Article|
|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||British journal of cancer|
|Date||2020 Aug 03|
|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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|LY3127804||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|
|Unknown unknown||Advanced Solid Tumor||not applicable||LY3127804 + Ramucirumab||Phase I||Actionable||In a Phase I trial, the combination treatment of LY3127804 and Cyramza (ramucirumab) at various doses in advanced solid tumor patients demonstrated safety and was well-tolerated, and led to a best overall response of partial responses observed in four patients, including one each with clear cell endometrial carcinoma, cervix squamous cell carcinoma, carcinoma of unknown primary, and gastroesophageal junction adenocarcinoma, and resulted in stable disease in 37% (13/35) (PMID: 32741971; NCT02597036).||32741971|
|Unknown unknown||Advanced Solid Tumor||not applicable||LY3127804||Phase I||Actionable||In a Phase I trial, treatment with LY3127804 in advanced solid tumor patients demonstrated safety and was well-tolerated, and resulted in stable disease in 55% (11/20) of patients (PMID: 32741971).||32741971|