PMID- 33105036 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 26 IP - 4 DP - 2021 Apr TI - A Phase I Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors. PG - e549-e566 LID - 10.1002/onco.13577 [doi] AB - LESSONS LEARNED: The 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. BACKGROUND: This 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). METHODS: Of 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. RESULTS: Ipilimumab 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). CONCLUSION: Ipilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations. CI - (c) AlphaMed Press; the data published online to support this summary are the property of the authors. FAU - Ma, Yuxiang AU - Ma Y AD - Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Fang, Wenfeng AU - Fang W AD - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of China. FAU - Zhao, Hongyun AU - Zhao H AD - Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China. FAU - Bathena, Sai Praneeth AU - Bathena SP AD - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA. FAU - Tendolkar, Amol AU - Tendolkar A AD - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA. FAU - Sheng, Jennifer AU - Sheng J AD - Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Lawrenceville, New Jersey, USA. FAU - Zhang, Li AU - Zhang L AD - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, People's Republic of China. LA - eng SI - ClinicalTrials.gov/NCT02516527 PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201111 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Ipilimumab) SB - IM MH - China MH - Humans MH - Ipilimumab/adverse effects MH - *Melanoma/drug therapy MH - *Nasopharyngeal Neoplasms MH - Neoplasm Recurrence, Local PMC - PMC8018307 OTO - NOTNLM OT - Ipilimumab OT - Melanoma OT - Nasopharyngeal carcinoma EDAT- 2020/10/27 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/04/01 CRDT- 2020/10/26 17:16 PHST- 2020/06/24 00:00 [received] PHST- 2020/10/16 00:00 [accepted] PHST- 2020/10/27 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/26 17:16 [entrez] PHST- 2021/04/01 00:00 [pmc-release] AID - ONCO13577 [pii] AID - 10.1002/onco.13577 [doi] PST - ppublish SO - Oncologist. 2021 Apr;26(4):e549-e566. doi: 10.1002/onco.13577. Epub 2020 Nov 11.