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

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.

KEYWORDS:

• (5-8): advanced non-small cell lung cancer
• epidermal growth factor receptor
• PF-06747775
• phase 1/2 study
• tyrosine kinase inhibitor

Acknowledgments

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.

Declaration of interest

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.

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.

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.

Timothy F Burns: consulting and/or advisory board roles for Novartis, Foundation Medicine Inc., Amgen, and Mirati Therapeutics Inc.

Zarnie Lwin: honoraria for Astra Zeneca, Roche; advisory board for AbbVie; consulting role for MSD, Merck; travel and educational support from BMS.

Nuzhat Pathan, Wei Dong Ma, Joanna C Masters, Nandini Cossons, and Keith Wilner: employees and shareholders of Pfizer.

Makoto Nishio: grants and/or personal fees from Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer-Ingelheim, MSD, Novartis, Merck Biopharma, Daiichi Sankyo, Takeda Pharmaceutical Company Limited, TEIJIN PHARMA LIMITED, and AbbVie.

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.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

All authors were involved in the trial conception/design, or the acquisition, analysis, or interpretation of data. All authors contributed to the drafting of the manuscript. The manuscript has been read and approved by all the authors, and all the conditions as previously stated by the ICMJE have been met. All authors agree to be accountable for all aspects of the work.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This paper was funded by Pfizer.