PMID- 34268711 OWN - NLM STAT- MEDLINE DCOM- 20220217 LR - 20240229 IS - 1573-0646 (Electronic) IS - 0167-6997 (Linking) VI - 39 IP - 6 DP - 2021 Dec TI - A phase I study of IMC-001, a PD-L1 blocker, in patients with metastatic or locally advanced solid tumors. PG - 1624-1632 LID - 10.1007/s10637-021-01078-6 [doi] AB - Introduction IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). This study evaluated the safety, pharmacokinetics, and pharmacodynamics of IMC-001 in patients with advanced solid tumors. Materials and Methods This open-labeled phase I study used a standard 3 + 3 dose-escalation design, with doses ranging from 2 to 20 mg/kg. IMC-001 was administered intravenously every 2 weeks until disease progression or unacceptable toxicity. The dose-limiting toxicity window was defined as 21 days from the first dose. Results Fifteen subjects were included in 5 dose-escalation cohorts. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common adverse events (AEs) were general weakness, decreased appetite, fever, and cough. No grade 4 or 5 treatment emergent AEs were reported during the study. One subject in the 2 mg/kg cohort showed grade 2 immune-induced thyroiditis and diabetes mellitus suspected to be related to IMC-001. Over the dose range of 2-20 mg/kg IMC-001, the AUC(0-14d), AUC(0-infinity), and C(max) generally increased in a dose-proportional manner for each step of dose escalation. Of the 15 enrolled patients, 1 subject with rectal cancer showed a partial response, and the disease control rate was 33.3%. Conclusions IMC-001 demonstrated a favorable safety profile up to 20 mg/kg administered intravenously every 2 weeks and showed preliminary efficacy in patients with advanced solid tumors. Based on pharmacokinetic and pharmacodynamic data, 20 mg/kg was selected as the recommended phase II dose. Clinical trial identification NCT03644056 (date of registration: August 23, 2018). CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Keam, Bhumsuk AU - Keam B AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. FAU - Ock, Chan-Young AU - Ock CY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. FAU - Kim, Tae Min AU - Kim TM AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. FAU - Oh, Do-Youn AU - Oh DY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. FAU - Kang, Won Ki AU - Kang WK AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. FAU - Park, Yeon Hee AU - Park YH AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. FAU - Lee, Jeeyun AU - Lee J AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. FAU - Lee, Ji Hye AU - Lee JH AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Ahn, Yoen Hee AU - Ahn YH AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Kim, Hyeon Ju AU - Kim HJ AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Chang, Sook Kyung AU - Chang SK AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Park, Jihyun AU - Park J AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Choi, Ji Yea AU - Choi JY AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Song, Yun Jeong AU - Song YJ AD - ImmuneOncia Therapeutics Inc., Seongnam, South Korea. FAU - Park, Young Suk AU - Park YS AUID- ORCID: 0000-0001-8769-3556 AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. pys27hmo@skku.edu. LA - eng SI - ClinicalTrials.gov/NCT03644056 PT - Clinical Trial, Phase I PT - Journal Article DEP - 20210716 PL - United States TA - Invest New Drugs JT - Investigational new drugs JID - 8309330 RN - 0 (Antineoplastic Agents) RN - 0 (B7-H1 Antigen) RN - 0 (IMC-001) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics MH - Area Under Curve MH - B7-H1 Antigen/antagonists & inhibitors MH - Dose-Response Relationship, Drug MH - Maximum Tolerated Dose MH - Neoplasm Metastasis MH - *Neoplasms/drug therapy/pathology MH - *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects/pharmacokinetics OTO - NOTNLM OT - IMC-001 OT - Immunotherapy OT - PD-L1 OT - Phase I study OT - Solid tumor EDAT- 2021/07/17 06:00 MHDA- 2022/02/17 06:00 CRDT- 2021/07/16 06:50 PHST- 2021/01/28 00:00 [received] PHST- 2021/01/31 00:00 [accepted] PHST- 2021/07/17 06:00 [pubmed] PHST- 2022/02/17 06:00 [medline] PHST- 2021/07/16 06:50 [entrez] AID - 10.1007/s10637-021-01078-6 [pii] AID - 10.1007/s10637-021-01078-6 [doi] PST - ppublish SO - Invest New Drugs. 2021 Dec;39(6):1624-1632. doi: 10.1007/s10637-021-01078-6. Epub 2021 Jul 16.