PMID- 34795408
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20221024
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 126
IP  - 4
DP  - 2022 Mar
TI  - Phase 1A/1B dose-escalation and -expansion study to evaluate the safety, 
      pharmacokinetics, food effects and antitumor activity of pamiparib in advanced 
      solid tumours.
PG  - 576-585
LID - 10.1038/s41416-021-01632-2 [doi]
AB  - BACKGROUND: Pamiparib, a PARP1/2 inhibitor, demonstrated antitumor activity in 
      preclinical models. METHODS: This Phase 1A/1B dose-escalation/dose-expansion 
      study enrolled adults (>/=18 years) with advanced/metastatic cancer. The 
      dose-escalation phase evaluated the recommended Phase 2 dose (RP2D), maximum 
      tolerated dose (MTD), and pharmacokinetics; the dose-expansion phase evaluated 
      the antitumor activity and food effects. RESULTS: Patients (N = 101) were 
      enrolled in dose-escalation (n = 64) and dose-expansion (n = 37). During BID 
      dose-escalation, dose-limiting toxicities were Grade 2 nausea (n = 1, 40 mg; 
      n = 1, 80 mg); Grade 2 nausea and Grade 2 anorexia (n = 1, 120 mg), Grade 2 
      nausea, Grade 3 fatigue and Grade 3 paraesthesia (n = 1, 120 mg); MTD was 80 mg 
      BID and RP2D was 60 mg BID. Common adverse events (AEs) were nausea (69.3%), 
      fatigue (48.5%) and anaemia (35.6%); the most common Grade >/=3 AE was anaemia 
      (24.8%). There was a dose-proportional increase in pamiparib exposure; no food 
      effects on pharmacokinetics were observed. In the efficacy-evaluable population 
      (n = 77), objective response rate (ORR) was 27.3% (95% CI, 17.7-38.6%). Median 
      duration of response was 14.9 months (95% CI, 8.7-26.3). In the epithelial 
      ovarian cancer (EOC)-evaluable population (n = 51), ORR was 41.2% (95% CI, 
      27.6-55.8%). CONCLUSIONS: Pamiparib was tolerated with manageable AEs, and 
      antitumor activity was observed in patients with EOC. CLINICALTRIALS. GOV 
      IDENTIFIER: NCT02361723.
CI  - (c) 2021. The Authors.
FAU - Lickliter, Jason D
AU  - Lickliter JD
AD  - Nucleus Network, Melbourne, VIC, Australia.
FAU - Voskoboynik, Mark
AU  - Voskoboynik M
AD  - Nucleus Network, Melbourne, VIC, Australia.
AD  - Central Clinical School, Monash University, Melbourne, VIC, Australia.
FAU - Mileshkin, Linda
AU  - Mileshkin L
AD  - Peter MacCallum Cancer Centre-East Melbourne, East Melbourne, VIC, Australia.
FAU - Gan, Hui K
AU  - Gan HK
AD  - Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, 
      Heidelberg, Melbourne, VIC, Australia.
AD  - La Trobe University School of Cancer Medicine, Heidelberg, VIC, Australia.
AD  - Department of Medicine, University of Melbourne, Heidelberg, VIC, Australia.
FAU - Kichenadasse, Ganessan
AU  - Kichenadasse G
AUID- ORCID: 0000-0001-9923-5149
AD  - Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, 
      SA, Australia.
FAU - Zhang, Kathy
AU  - Zhang K
AD  - BeiGene USA, Inc., San Mateo, CA, USA.
FAU - Zhang, Maggie
AU  - Zhang M
AD  - BeiGene USA, Inc., San Mateo, CA, USA.
FAU - Tang, Zhiyu
AU  - Tang Z
AD  - BeiGene USA, Inc., San Mateo, CA, USA.
FAU - Millward, Michael
AU  - Millward M
AUID- ORCID: 0000-0002-1744-1617
AD  - Linear Clinical Research & University of Western Australia, Nedlands, WA, 
      Australia. michael.millward@uwa.edu.au.
LA  - eng
SI  - ClinicalTrials.gov/NCT02361723
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211118
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Fluorenes)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 8375F9S90C (pamiparib)
SB  - IM
EIN - Br J Cancer. 2021 Dec 20;:. PMID: 34931042
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Fluorenes/*administration & dosage/adverse effects/pharmacokinetics
MH  - Food
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC8854719
COIS- Dr. JDL has no competing interests to declare. Dr. MV reports personal fees from 
      Merck Sharp & Dohme and personal fees from AstraZeneca outside the submitted 
      work. Dr. LM reports other support from BeiGene outside the submitted work. Dr. 
      HG reports personal fees from Merck Serono, Eisai, and Bristol-Myers Squibb 
      outside the submitted work. Dr. GK has nothing to disclose. Dr. KZ, Dr. MZ and 
      Dr. ZT are employees with stock grant or options in BeiGene, Ltd. Dr. MM reports 
      personal fees and non-financial support from AstraZeneca, Bristol-Myers Squibb, 
      and Roche; and personal fees from Merck Sharp & Dohme, Pfizer and Novartis 
      outside the submitted work.
EDAT- 2021/11/20 06:00
MHDA- 2022/03/11 06:00
PMCR- 2021/11/18
CRDT- 2021/11/19 06:49
PHST- 2021/07/19 00:00 [received]
PHST- 2021/11/03 00:00 [accepted]
PHST- 2021/10/25 00:00 [revised]
PHST- 2021/11/20 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/11/19 06:49 [entrez]
PHST- 2021/11/18 00:00 [pmc-release]
AID - 10.1038/s41416-021-01632-2 [pii]
AID - 1632 [pii]
AID - 10.1038/s41416-021-01632-2 [doi]
PST - ppublish
SO  - Br J Cancer. 2022 Mar;126(4):576-585. doi: 10.1038/s41416-021-01632-2. Epub 2021 
      Nov 18.