Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 747-757 |
| Number of pages | 11 |
| Journal | Expert Opinion on Investigational Drugs |
| Volume | 31 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2022 |
Bibliographical note
Funding Information:Medical writing support was provided by Anne Marie McGonigal, PhD, of Engage Scientific Solutions and funded by Pfizer.
Funding Information:
Byoung Chul Cho: institutional research funding from Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, and MSD; consulting roles for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, and MSD; stock ownership of TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics; and royalties from Champions Oncology.
Funding Information:
Dong-Wan Kim: institutional research funding from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, GSK; Travel and accommodation support for advisory board meeting attendance from Amgen, Daiichi-Sankyo.
Funding Information:
Sarah B Goldberg: research funding from AstraZeneca and Boehringer Ingelheim; consulting/advisory board for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi-Sankyo, Regeneron, Takeda and Janssen.
Funding Information:
This paper was funded by Pfizer. Medical writing support was provided by Anne Marie McGonigal, PhD, of Engage Scientific Solutions and funded by Pfizer. Data from this study has been published/presented at the following congresses as an abstract and/or poster/oral presentation: European Society for Medical Oncology 42nd Congress–ESMO 2017; UC San Diego Moores Cancer Center–13th Industry/Academia Translational Oncology Symposium 2017; IASLC Targeted Therapies of Lung Cancer 2017.
Funding Information:
Hatim Husain: institutional research funding from BMS, Eli Lilly, Roche Sequencing Solutions, Pfizer; consulting or advisory roles for Takeda, Blueprints Medicine, AstraZeneca, Mirati, Foundation Medicine, Philips, Coherus, Merck; Honoraria from AstraZeneca, Blueprints Medicine, Janssen.
Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
