PMID- 37858184
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231119
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Oct 20
TI  - Combination of GT90001 and nivolumab in patients with advanced hepatocellular 
      carcinoma: a multicenter, single-arm, phase 1b/2 study.
PG  - 395
LID - 10.1186/s12916-023-03098-w [doi]
LID - 395
AB  - BACKGROUND: GT90001 (also known as PF-03446962) is an anti-ALK-1 monoclonal 
      antibody and has shown activity in hepatocellular carcinoma (HCC). This phase 
      1b/2 study was designed to determine the recommended phase 2 dose (RP2D) of 
      GT90001 plus nivolumab, and assess the safety and anti-tumor activity in patients 
      with advanced HCC. METHODS: Patients with advanced HCC were recruited from 3 
      centers. Eligible patients in the dose de-escalation stage received the GT90001 
      on day 1 of a 14-day cycle in a rolling-six design with a fixed dose of nivolumab 
      (3.0 mg/kg). Patients in dose-expansion stage received the RP2D of GT90001 plus 
      nivolumab. Primary endpoint was safety. Key secondary endpoint was objective 
      response rate (ORR) as per RECIST 1.1. RESULTS: Between July 9, 2019, and August 
      8, 2022, 20 patients were treated (6 in phase 1b; 14 in phase 2) and evaluable 
      for analysis. In phase 1b, no dose-limiting toxicities were observed, and GT90001 
      7.0 mg/kg was confirmed as the RP2D. Common grade 3/4 adverse events (AEs) were 
      platelet count decreased (15%). No deaths due to AEs were reported. Confirmed ORR 
      and disease control rate were 30% (95% CI, 14.6%-51.9%) and 40% (95% CI, 
      21.9%-61.3%), respectively. Median duration of response was not calculated (95% 
      CI, 7.39 months to not calculated). Median progression-free survival (PFS) was 
      2.81 months (95% CI, 1.71-9.33), with 6-month and 12-month PFS rates of 35% and 
      25%, respectively. One patient with multiple intra- and extra-hepatic metastases 
      was diagnosed with pseudo-progression upon GT90001 plus nivolumab exposure. 
      CONCLUSIONS: GT90001 plus nivolumab has a manageable safety profile and promising 
      anti-tumor activity in patients with advanced HCC. TRIAL REGISTRATION NUMBER: 
      ClinicalTrials.gov identifier NCT03893695.
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Hsu, Chiun
AU  - Hsu C
AD  - Department of Medical Oncology, National Taiwan University Cancer Center, No. 57, 
      Ln. 155, Sec. 3, Keelung Road., Da'an Dist., Taipei, 106, Taiwan. 
      hsuchiun@ntu.edu.tw.
AD  - Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan 
      South Road, Taipei, 100, Taiwan. hsuchiun@ntu.edu.tw.
FAU - Chang, Yi-Fang
AU  - Chang YF
AD  - Department of Hematology and Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
FAU - Yen, Chia-Jui
AU  - Yen CJ
AD  - Department of Oncology, National Cheng Kung University Hospital, College of 
      Medicine, National Cheng Kung University, Taipei, Taiwan.
FAU - Xu, Yu-Wei
AU  - Xu YW
AD  - Suzhou Kintor Pharmaceuticals, Inc., Suzhou, China.
FAU - Dong, Min
AU  - Dong M
AD  - Suzhou Kintor Pharmaceuticals, Inc., Suzhou, China.
FAU - Tong, You-Zhi
AU  - Tong YZ
AD  - Suzhou Kintor Pharmaceuticals, Inc., Suzhou, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT03893695
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20231020
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Humans
MH  - Nivolumab/adverse effects
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - *Liver Neoplasms/drug therapy
MH  - Progression-Free Survival
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
PMC - PMC10588186
OTO - NOTNLM
OT  - Anti-angiogenic therapy
OT  - GT90001
OT  - Hepatocellular carcinoma
OT  - Immunotherapy
OT  - Nivolumab
OT  - PF-03446962
COIS- The authors declare that they have no conflict of interest.
EDAT- 2023/10/20 06:42
MHDA- 2023/10/23 01:18
PMCR- 2023/10/20
CRDT- 2023/10/20 00:03
PHST- 2023/05/18 00:00 [received]
PHST- 2023/09/28 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/20 06:42 [pubmed]
PHST- 2023/10/20 00:03 [entrez]
PHST- 2023/10/20 00:00 [pmc-release]
AID - 10.1186/s12916-023-03098-w [pii]
AID - 3098 [pii]
AID - 10.1186/s12916-023-03098-w [doi]
PST - epublish
SO  - BMC Med. 2023 Oct 20;21(1):395. doi: 10.1186/s12916-023-03098-w.