UNASSIGNED: 5561 Background: PF is a potent, irreversible small molecule pan-HER @entity4149 kinase inhibitor (TKI) with pre-clinical antitumor activity against EGFRvIII-mutated cell lines and xenograft models resistant to reversible @entity470 TKIs. METHODS: Eligible @entity1 (pts) had untreated RM @entity213 with measurable disease and no prior anti- @entity470 therapy. Paired biopsies as feasible were done for biomarkers; plasma was collected for PK. PF is administered at 45 mg p.o. every day in 21-day cycles. Primary endpoint is objective response rate (ORR), assessed every 6 weeks by RECIST 1.1. A Simon 2-stage trial design with H0: ORR <=  5% and Ha: ORR >=  15% stipulated that >=  2 responses must be observed in first 23 evaluable pts to proceed to stage II, >=  6 responses in first 56 evaluable pts to meet primary objective. RESULTS: 69 pts are enrolled: median age 62 years (range: 40-82); M:F (%)= 88:12; ECOG 0:1:2 (%) = 30:64:6; prior radiation = 93%; prior chemotherapy = 46%; ex-smoker/current smoker = 86%. In 68 pts evaluable for @entity137 , treatment-related adverse events (TRAEs) led to drug discontinuation in 7 (10%), dose reduction in 19 (28%) and interruption in 26 (38%). The most frequent grade 1 and 2 TRAEs were (% of pts): @entity294 (71%), @entity1909 (63%), dry skin (44%), @entity3136 (32%), @entity1295 (31%), @entity111 (28%) and hand-foot reaction (26%). Gr 3 TRAEs > 3% included: @entity294 (13%), @entity1295 (9%), @entity1909 (7%) and hand-foot reaction (4%). Among the first 56 evaluable pts, 6 pts (11%) achieved a partial response (median duration = 4.3 months); 35 pts (63%) had stable disease, of which 6 pts (11%) maintained disease stabilization >=  24 weeks. Data for all 69 pts at time of submission: median PFS = 2.8 months (95% C.I. 2.6-4.1 months), 6-month PFS =15% (95% C.I. 5-29%), and median survival = 7.6 months (95% C.I. 6.4-12 months). PK and biomarker analyses will be presented. CONCLUSIONS: Primary endpoint was met and @entity137 profile was manageable. Antitumor activity of PF is consistent with @entity470 TKIs, with ongoing molecular characterization of EGFRvIII mutations to evaluate potential as a biomarker of clinical activity.

Phase II trial of the irreversible oral pan- @entity1 EGF receptor (HER) inhibitor PF-00299804 (PF) as first-line treatment in recurrent and/or metastatic (RM) XXXX ( @entity213 ).

@entity1 :: ('9606', 'Species') :: ['patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity3136 :: ('MESH:D013280', 'Disease') :: ['stomatitis'] @entity470 :: ('1956', 'Gene') :: ['EGFR'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity1295 :: ('MESH:D005221', 'Disease') :: ['fatigue'] @entity111 :: ('MESH:D011537', 'Disease') :: ['pruritis'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity1909 :: ('MESH:D003872', 'Disease') :: ['dermatitis acneiform'] @entity213 :: ('MESH:C535575', 'Disease') :: ['SCCHN']
@entity213 :: (MESH:C535575,Disease) :: ['squamous cell carcinoma of the head and neck']
