1358P - First-In-Human Phase I Study of PF-06747775, a Third Generation Mutant Selective EGFR Tyrosine Kinase Inhibitor (TKI) in Metastatic EGFR Mutant NSC...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Clinical Research
Cancers in Adolescents and Young Adults (AYA)
Thoracic Malignancies
Non-Small Cell Lung Cancer
Basic Scientific Principles
Presenter Hatim Husain
Citation Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380
Authors H. Husain1, R.G. Martins2, S.B. Goldberg3, P. Senico4, W. Ma5, J. Masters6, N. Pathan6, D. Kim7, M.A. Socinski8, Z. Goldberg5, B.C. Cho9
  • 1Medicine, UC San Diego Moores Cancer Center, 92093 - San Diego/US
  • 2Oncology/hematology, Seattle Cancer Care Alliance, Seattle/US
  • 3Medical Oncology, Yale Cancer Center, New Haven/US
  • 4Oncology, Pfizer, Collegeville/US
  • 5Oncology, Pfizer, New York/US
  • 6Oncology, Pfizer, La Jolla/US
  • 7Oncology, Seoul National University Hospital, Seoul/KR
  • 8Oncology, University of Pittsburgh, Pittsburgh/US
  • 9Oncology, Yonsei Cancer Center, Yonsei/KR

Abstract

Background

PF-06747775 (“PF-7775”) is a selective, 3rd generation Epidermal Growth Factor Receptor (EGFR) TKI effective against EGFR sensitizing and T790M mutations in preclinical models. Enrollment was completed in a phase I study of PF-7775 in EGFR mutant (EGFRm+) NSCLC patients (pts) who progressed after a prior EGFR TKI.

Methods

EGFRm+ NSCLC pts with resistance to first-line EGFR-TKIs enrolled in a multicenter trial in 6 dose escalation (25 mg–600 mg) and 2 dose expansion cohorts (200 mg and 300 mg). Biopsy for EGFR T790M at clinical progression was not required for study entry. PF-7775 was given orally once daily. All pts were assessed for response, adverse events (AEs), and pharmacokinetics. Plasma T790M testing was conducted retrospectively.

Results

As of a 3 Feb17 data cutoff, 44 pts were enrolled (59% female, median age 63.5, Asian/Caucasian 73/25%).The most common all grade AEs in all enrolled patients (≥ 25%) were: diarrhea (57%), rash (59%), paronychia (52%), dermatitis acneiform (34%), stomatitis (32%), pruritus (27%), dry skin (25%), and rhinorrhea (25%). Grade 3 events were consistent with known EGFR TKI toxicities (diarrhea and skin toxicity) and easily managed. No grade 4 treatment related AEs were noted in dose escalation or expansion. Nineteen pts (43%) had dose reductions due to treatment related AEs at the higher dose cohorts and the RP2D of 200 mg was selected based on the AE profile and tolerability of drug at this dose for longer term administration. The prevalence rate of T790M, L858R, and del 19 in plasma samples, along with data correlating ORR (CR and PR rate) and CBR (CR + PR + SD) is ongoing.

Conclusions

PF-7775 is well tolerated at 200 mg dose in EGFRm+ NSCLC pts with acquired resistance to first-line EGFR-TKIs. Data relating mutational status to response rate in plasma is ongoing.

Clinical trial identification

NCT02349633

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

P. Senico, W. Ma, J. Masters, N. Pathan, Z. Goldberg: Employee of Pfizer and declare Pfizer stock ownership. B.C. Cho: Conducting Pfizer corporate-sponsored research. All other authors have declared no conflicts of interest.