Efficacy and safety of PF-00299804 (PF299), an oral, irreversible, pan-human epidermal growth factor receptor (pan-HER) tyrosine kinase inhibitor (TKI), as first-line treatment (tx) of selected patients (pts) with advanced (adv) non-small cell lung cancer (NSCLC).

Abstract

7537 Background: Efficacy of gefitinib as first-line tx of adv NSCLC with epidermal growth factor receptor (EGFR) mutation (mu) has been shown in a phase (P) 3 trial. PF299 shows preclinical activity in EGFR-mutant NSCLC, including T790M (a secondary resistance mu arising in ∼50% of pts after EGFR TKI benefit). This open-label, single-stage P2 study evaluates efficacy and safety of first-line PF299 in a pt population with adv NSCLC, molecularly selected or clinically enriched for EGFR mu. Methods: Pts with adv adenocarcinoma of lung and no prior systemic tx for adv NSCLC are eligible if they are non/light smokers or known to have EGFR mu. Tissue is requested from all pts. Pts receive PF299 45 mg continuously once daily and are assessed every 28 days. Endpoints include: progression-free survival at 4 months (PFS4m; primary), tumor response, safety, serial pharmacokinetics, and tissue- and blood-based biomarkers, including T790M mu. Planned enrolment is ∼80 pts, including ≥ 30 each of Asian and of non-Asian ethnicity. Results: To date, 39 pts have enrolled (23 female; 23 Asian). Of 29 evaluable pts, 1 had a complete response, 6 a partial response, and 16 stable disease ≥ 6 weeks. Preliminary PFS rates at 3, 4, and 6 m were 90%, 79%, and 79%, respectively. Mu status was obtained in 31/39 pts. All evaluable pts with known EGFR mutant NSCLC (n = 14) showed tumor shrinkage. Common tx-related adverse event (AEs) were diarrhea (79%; grade 3; 9%), dermatitis acneiform (49%; 9%), stomatitis (42%; 6%), acne (24%; 0%), rash (21%; 0%), and anorexia (18%; 0%). One pt discontinued due to AE; 10 required dose reduction while remaining on study. Conclusions: Preliminary data suggest PF299 demonstrates encouraging efficacy as first-line tx of selected Asian and non-Asian pts with NSCLC, as reflected by PFS rates. Of note, tumor shrinkage was seen in all evaluable pts with EGFR mutant disease. AEs were mostly grade 1/2 and manageable; however, to ensure long term tolerability, a lower starting dose is being considered. Clinical follow-up and biomarker data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer AstraZeneca, AVEO, Boehringer Ingelheim, Eisai, Genentech, Lilly, Merck Serono, OSI Pharmaceuticals, Pfizer, Roche, Syndax Pharmaceuticals Gatekeeper Pharmaceuticals, Pfizer AstraZeneca, Genentech, Lilly, Pfizer, Roche, sanofi-aventis Abraxis BioScience, Celgene, Genentech, Lilly, Pfizer Genzyme