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Phase I Dose-Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors.

ABSTRACT: Ramucirumab was well tolerated in Chinese patients with advanced solid tumors, and adverse events were manageable in this study.Pharmacokinetics characteristics in Chinese patients were similar to those in other populations. Immunogenicity was not detected.No efficacy conclusion could be drawn, and further randomized studies are warranted.This single-arm, nonrandomized, open-label, dose-escalation, phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ramucirumab in Chinese patients with advanced solid tumors that were resistant to standard therapy or no standard therapy was available.Dose escalation was a 3?+?3 design, with expansion in Cohorts 2 and 3 for PK. Ramucirumab was given intravenously at three different dosages: 6 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 8 mg/kg every 2 weeks. Safety analyses included all patients. PK, immunogenicity, and antitumor activity were also assessed.Among 28 patients treated, 2 experienced dose-limiting toxicity, possibly related to ramucirumab. No maximum tolerated dose was determined. All patients experienced at least one treatment-emergent adverse event. Grade ?3 adverse event was reported for 53.6% (n?=?15) of patients. PK analyses indicated that ramucirumab had low clearance, small volume of distribution, and long half-life in Chinese patients, as in other populations. Immunogenicity was not detected. No patient had complete/partial response, and 64.3% (n?=?18) had stable disease with a median duration of 5.55 months (95% confidence interval: 3.38-7.13 months).Ramucirumab appeared to be well tolerated in Chinese patients with advanced solid tumors. PK characteristics in Chinese patients were similar to those in other populations.

SUBMITTER: Cao J

PROVIDER: S-EPMC5469595 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Phase I Dose-Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors.

Cao Junning J Ji Dongmei D Chen Zhiyu Z Shen Weina W Wang Jin J Li Baoyue B Chi Haidong H Long Amanda A Gao Ling L Li Jin J

The oncologist 20170502 6

<h4>Lessons learned</h4>Ramucirumab was well tolerated in Chinese patients with advanced solid tumors, and adverse events were manageable in this study.Pharmacokinetics characteristics in Chinese patients were similar to those in other populations. Immunogenicity was not detected.No efficacy conclusion could be drawn, and further randomized studies are warranted.<h4>Background</h4>This single-arm, nonrandomized, open-label, dose-escalation, phase I study was designed to evaluate the safety, tole ...[more]

PMID: 28465370

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Project description:Lessons learnedThe overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified. The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.BackgroundThis phase I, open-label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as "other." During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3-week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12-week cycle, to a maximum of 3 years or PD. Considering the co-primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose-limiting toxicities during the 42-day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1-2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti-ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.

Dataset Information

Phase I Dose-Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors.

Publications

Phase I Dose-Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors.

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