PMID- 35657653
OWN - NLM
STAT- MEDLINE
DCOM- 20220713
LR  - 20220715
IS  - 1744-7658 (Electronic)
IS  - 1354-3784 (Linking)
VI  - 31
IP  - 7
DP  - 2022 Jul
TI  - A phase 1b/2 study of PF-06747775 as monotherapy or in combination with 
      Palbociclib in patients with epidermal growth factor receptor mutant advanced 
      non-small cell lung cancer.
PG  - 747-757
LID - 10.1080/13543784.2022.2075341 [doi]
AB  - INTRODUCTION: This Phase 1/2 study (NCT02349633) explored the safety and 
      antitumor activity of PF-06747775 (oral, third-generation epidermal growth factor 
      receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced non-small 
      cell lung cancer after progression on an EGFR inhibitor. METHODS: Phase 1 was a 
      dose-escalation study of PF-06747775 monotherapy (starting dose: 25 mg once daily 
      [QD]). Phase 1b/2 evaluated PF-06747775 monotherapy at recommended Phase 2 dose 
      (RP2D; Cohort 1); PF-06747775 200 mg QD plus palbociclib (starting dose: 100 mg 
      QD orally; Cohort 2A); and PF-06747775 monotherapy at RP2D in a Japanese lead-in 
      cohort. RESULTS: Sixty-five patients were treated. Median treatment duration was 
      40.1 weeks. Monotherapy maximum tolerated dose was not determined. Two patients 
      in Cohort 2A had dose-limiting toxicities. The monotherapy RP2D was estimated to 
      be 200 mg QD. Most frequently reported adverse events (AEs) were diarrhea 
      (69.2%), paronychia (69.2%), and rash (60.0%). Most AEs were grades 1-3. Overall, 
      objective response rate (90% confidence interval [CI]) was 41.5% (31.2-52.5%). 
      Median (range) duration of response was 11.09 (2.70-34.57) months. Median 
      progression-free survival (90% CI) was 8.1 (5.4-23.3) months. CONCLUSIONS: 
      PF-06747775 had a manageable safety profile and the study design highlights 
      important considerations for future anti-EGFR agent development.
FAU - Cho, Byoung Chul
AU  - Cho BC
AD  - Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of 
      Korea.
FAU - Goldberg, Sarah B
AU  - Goldberg SB
AD  - Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
FAU - Kim, Dong-Wan
AU  - Kim DW
AD  - Cancer Research Institute, Seoul National University College of Medicine and 
      Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Socinski, Mark A
AU  - Socinski MA
AD  - Thoracic Oncology, Advent Health Cancer Institute, Orlando, FL, USA.
FAU - Burns, Timothy F
AU  - Burns TF
AD  - Department of Medicine, University of Pittsburgh Medical Center Hillman Cancer 
      Center, Pittsburgh, PA, USA.
FAU - Lwin, Zarnie
AU  - Lwin Z
AD  - Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
FAU - Pathan, Nuzhat
AU  - Pathan N
AD  - Translational Oncology, Pfizer Inc, San Diego, CA, USA.
FAU - Ma, Wei Dong
AU  - Ma WD
AD  - Biostatistics, Pfizer Inc, New York, USA.
FAU - Masters, Joanna C
AU  - Masters JC
AD  - Translational Oncology, Pfizer Inc, San Diego, CA, USA.
FAU - Cossons, Nandini
AU  - Cossons N
AD  - Lead Study Clinician, Pfizer Inc, UK.
FAU - Wilner, Keith
AU  - Wilner K
AD  - Translational Oncology, Pfizer Inc, San Diego, CA, USA.
FAU - Nishio, Makoto
AU  - Nishio M
AD  - Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese 
      Foundation for Cancer Research, Tokyo, Japan.
FAU - Husain, Hatim
AU  - Husain H
AD  - Department of Medicine, UCSD Moores Cancer Center, La Jolla, CA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20220603
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - G9ZF61LE7G (palbociclib)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - ErbB Receptors/genetics
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Piperazines/therapeutic use
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Pyridines
OTO - NOTNLM
OT  - (5-8): advanced non-small cell lung cancer
OT  - PF-06747775
OT  - epidermal growth factor receptor
OT  - phase 1/2 study
OT  - tyrosine kinase inhibitor
EDAT- 2022/06/04 06:00
MHDA- 2022/07/14 06:00
CRDT- 2022/06/03 11:53
PHST- 2022/06/04 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/03 11:53 [entrez]
AID - 10.1080/13543784.2022.2075341 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2022 Jul;31(7):747-757. doi: 
      10.1080/13543784.2022.2075341. Epub 2022 Jun 3.