Abstract CT158: Phase I study of ramucirumab, a recombinant human IgG1 monoclonal antibody inhibiting vascular endothelial growth factor receptor-2, in Chinese patients with advanced solid tumors
Authors: Li Jin , Cao Junning , Wang Jin , Li Baoyue , Chi Haidong , Gao Ling 
Published: July 2016

Abstract
Background: Ramucirumab is a recombinant human IgG1, high-affinity, neutralizing monoclonal antibody specific for the human vascular endothelial growth factor receptor-2 (VEGFR-2), which potently blocks binding of VEGF to VEGFR-2. The clinical benefit of ramucirumab has been demonstrated in several Phase 3 studies in patients with gastric cancer, non-small cell lung cancer, or colorectal cancer. The primary objective of this Phase 1 trial was to establish the safety profile and pharmacokinetics (PK) of ramucirumab monotherapy, when administered to Chinese patients.
Patients and methods: This was a single-arm, non-randomized, open-label, dose-escalation, Phase 1 study in which ramucirumab was given intravenously every 2 or 3 weeks (Q2W or Q3W) to Chinese patients with advanced solid tumors that were resistant to standard therapy or for whom no standard therapy was available. Eligible patients were enrolled sequentially into three treatment cohorts. Dose escalation was based on 3+3 design, with expansion to 10 patients each in Cohort 2 and 3 for PK data if no maximum tolerated dose was determined after the first 3-6 patients.
Results: A total of 28 patients were treated with ramucirumab: 6 in Cohort 1 (6mg/kg Q2W), 10 in Cohort 2 (10mg/kg Q3W), 12 in Cohort 3 (8mg/kg Q2W). Male and female each comprised 50% of the patients, with a median age of 57-years old (ranged 37 to 68). Two patients experienced dose-limiting toxicity: 1 in Cohort 1 (Grade 3 proteinuria), 1 in Cohort 2 (Grade 3 alanine aminotransferase increased). Treatment emergent adverse events (TEAE) possibly related to study drug in any grade and more frequent than 20% included fatigue (64.3%), hypertension (53.6%), aspartate aminotransferase increased (42.9%), proteinuria (42.9%), alanine aminotransferase increased (39.3%), decreased appetite (28.6%), sinus bradycardia (25.0%), headache (25.0%), platelet count decreased (21.4%), mouth haemorrhage (21.4%), and epistaxis (21.4%). Grade ?3 AE possibly related to study drug were reported for 35.7% of the patients (n = 10), hypertension (25.0%) was the only one more frequent than 5%. Upper gastrointestinal haemorrhage occurred in one patient as serious adverse event (SAE). Ramucirumab PK characteristics were similar to other monoclonal IgG1 antibodies: low total body clearance (∼13-19 mL/h), small volume of distribution at steady state (∼3-4 L), and long apparent terminal elimination half-life (∼6-10 days). At the time of study completion, no patient had complete/partial response, 64.3% (n = 18) of the patients had stable disease with a median duration of 5.55 months (95% CI: 3.38 to 7.13 months).
Conclusion:Ramucirumab was well tolerated in Chinese patients with similar PK characteristics from previous studies. No efficacy conclusion can be drawn from this Phase 1 trial.
Citation Format: Jin Li, Junning Cao, Jin Wang, Baoyue Li, Haidong Chi, Ling Gao. Phase I study of ramucirumab, a recombinant human IgG1 monoclonal antibody inhibiting vascular endothelial growth factor receptor-2, in Chinese patients with advanced solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT158.