PMID- 34984540
OWN - NLM
STAT- MEDLINE
DCOM- 20220720
LR  - 20230916
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 71
IP  - 8
DP  - 2022 Aug
TI  - Safety, antitumor activity and biomarkers of sugemalimab in Chinese patients with 
      advanced solid tumors or lymphomas: results from the first-in-human phase 1 
      trial.
PG  - 1897-1908
LID - 10.1007/s00262-021-03102-3 [doi]
AB  - BACKGROUND: This first-in-human phase 1 trial is to evaluate the safety, 
      pharmacokinetics, preliminary efficacy, and biomarkers of sugemalimab, a 
      full-length, fully human anti-PD-L1 monoclonal antibody, in Chinese patients with 
      advanced malignancies. METHODS: Eligible patients with unresectable advanced or 
      metastatic solid tumors or lymphomas were enrolled in phase 1a to receive 
      sugemalimab following a modified 3 + 3 design. The primary endpoints included 
      safety, tolerability, and the recommended Phase 2 dose (RP2D). In phase 1b, 
      patients with 7 selected types of tumor received sugemalimab at the RP2D alone 
      (monotherapy cohorts) or in combination with standard-of-care (SOC) chemotherapy 
      (combination cohorts). The primary endpoint of phase 1b was investigator-assessed 
      objective response rate (ORR). RESULTS: As of 19 February 2020, 29 and 178 
      patients were treated in phase 1a and 1b, respectively. No dose-limiting 
      toxicities were observed in phase 1a, and the RP2D of sugemalimab was determined 
      as 1200 mg fixed dose once every 3 weeks. Sugemalimab-related adverse events 
      (AEs) were mostly (75.9%) grade 1-2 in phase 1a. Antitumor activity was observed 
      across dose levels with an ORR of 24.1%. In phase 1b, 15.9% and 40.4% of patients 
      in the monotherapy and combination cohorts, respectively, reported grade 3-5 
      sugemalimab-related AEs. Promising efficacy was observed in all combination 
      cohorts, with ORRs ranging from 47.6 to 75.0%. Exploratory biomarker analysis did 
      not indicate significant differences in responses at different PD-L1 
      expression/tumor mutation burden levels. CONCLUSIONS: Sugemalimab was 
      well-tolerated and showed promising antitumor activity as monotherapy or in 
      combination with SOC chemotherapy in advanced malignancies. This trial was 
      registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842.
CI  - (c) 2021. The Author(s).
FAU - Gong, Jifang
AU  - Gong J
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), Department of Gastrointestinal Oncology, Peking University 
      Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 
      100142, China.
FAU - Cao, Junning
AU  - Cao J
AD  - Department of Medical Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Zhang, Qingyuan
AU  - Zhang Q
AD  - Department of Mammary and Lymphatic Medical Oncology, Harbin Medical University 
      Cancer Hospital, Harbin, China.
FAU - Xu, Nong
AU  - Xu N
AD  - Department of Medical Oncology, The First Affiliated Hospital of Zhejiang 
      University, Hangzhou, China.
FAU - Zhao, Yanqiu
AU  - Zhao Y
AD  - Respiratory Department of Internal Medicine, Affiliated Cancer Hospital of 
      Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
FAU - Xing, Baocai
AU  - Xing B
AD  - Department of Hepatobiliary and Pancreatic Surgery, Peking University Cancer 
      Hospital & Institute, Beijing, China.
FAU - Miao, Zhanhui
AU  - Miao Z
AD  - Department of Oncology, The First Affiliated Hospital of Xinxiang Medical 
      University, Weihui, China.
FAU - Wu, Yilong
AU  - Wu Y
AD  - Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, 
      Guangzhou, China.
FAU - Pan, Hongming
AU  - Pan H
AD  - Department of Medical Oncology, Sir Run Run Shaw Hospital, Hangzhou, China.
FAU - Gao, Quanli
AU  - Gao Q
AD  - Department of Biotherapy, Affiliated Cancer Hospital of Zhengzhou University, 
      Henan Cancer Hospital, Zhengzhou, China.
FAU - Li, Xingya
AU  - Li X
AD  - Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Liu, Baorui
AU  - Liu B
AD  - Department of Oncology, Nanjing Drum Tower Hospital, Nanjing, China.
FAU - Li, Wei
AU  - Li W
AD  - Department of Oncology, The First Bethune Hospital of Jilin University, 
      Changchun, China.
FAU - Pei, Zhidong
AU  - Pei Z
AD  - Department of Oncology, Luoyang Central Hospital, Luoyang, China.
FAU - Xia, Hongqiang
AU  - Xia H
AD  - CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.
FAU - Qi, Qinzhou
AU  - Qi Q
AD  - CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.
FAU - Dai, Hangjun
AU  - Dai H
AD  - CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.
FAU - Shi, Qingmei
AU  - Shi Q
AD  - CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.
FAU - Yang, Jianxin
AU  - Yang J
AD  - CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.
FAU - Li, Jin
AU  - Li J
AD  - Department of Oncology, Shanghai East Hospital, Tongji University School of 
      Medicine, No. 150, Jimo Road, Pudong New District, Shanghai, 200120, China. 
      lijin@csco.org.cn.
FAU - Shen, Lin
AU  - Shen L
AUID- ORCID: 0000-0003-1134-2922
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education/Beijing), Department of Gastrointestinal Oncology, Peking University 
      Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 
      100142, China. shenlin@bjmu.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT03312842
GR  - No. 2017YFC1308900/National Key Research and Development Program of China/
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20220105
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Antibodies, Monoclonal/adverse effects/therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Biomarkers, Tumor
MH  - China
MH  - Humans
MH  - Immune Checkpoint Inhibitors/adverse effects/therapeutic use
MH  - *Lymphoma/drug therapy
MH  - *Neoplasms/pathology
PMC - PMC9293819
OTO - NOTNLM
OT  - Immunotherapy
OT  - PD-L1
OT  - Solid tumor
OT  - Sugemalimab
COIS- Dr. Y. Wu reported receiving honoraria from AstraZeneca, Eli Lilly and Company, 
      Pfizer, Roche, and Sanofi. H. Xia, Q. Qi, H. Dai, Q. Shi, and J. Yang are paid 
      employees of CStone Pharmaceuticals. Other authors declared no conflict of 
      interest.
EDAT- 2022/01/06 06:00
MHDA- 2022/07/22 06:00
PMCR- 2022/01/05
CRDT- 2022/01/05 06:03
PHST- 2021/05/25 00:00 [received]
PHST- 2021/10/27 00:00 [accepted]
PHST- 2022/01/06 06:00 [pubmed]
PHST- 2022/07/22 06:00 [medline]
PHST- 2022/01/05 06:03 [entrez]
PHST- 2022/01/05 00:00 [pmc-release]
AID - 10.1007/s00262-021-03102-3 [pii]
AID - 3102 [pii]
AID - 10.1007/s00262-021-03102-3 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2022 Aug;71(8):1897-1908. doi: 
      10.1007/s00262-021-03102-3. Epub 2022 Jan 5.