Randomized phase III trial of gemcitabine/cisplatin with or without PF-3512676 as first line treatment of advanced non-small cell lung cancer (NSCLC)

Abstract

8017 Background: Gemcitabine/cisplatin (GC) is standard first line therapy for patients (pts) with Stage IIIB/IV NSCLC. PF- 3512676 (PF-676) is an oligodeoxynucleotide toll-like receptor 9 (TLR9) agonist. In a randomized phase 2 trial, addition of PF-676 to first line taxane/platinum chemotherapy produced a higher objective response rate and a trend toward improved overall survival (OS) in pts with advanced NSCLC. Confirmatory phase 3 trials were subsequently conducted. Methods: Chemotherapy naïve pts with Stage IIIB (pleural effusion) or Stage IV NSCLC, ECOG PS 0 or 1, measurable disease, adequate bone marrow, renal and hepatic function, no pre- existing autoimmune disease, no brain metastases and no chronic systemic corticosteroid therapy were included. All pts received G (1250 mg/m2) on D1 and 8 and C (75mg/m2) on D1 of each 21 day cycle (max 6 cycles). In the investigational arm pts also received PF-676 (0.2 mg/kg) SC on D 8 and 15 of each chemotherapy cycle and weekly thereafter until progression. The primary endpoint was OS. Results: 839 pts were randomized (416 GC + PF-676, 423 GC) from Nov ‘05 to Dec ‘06. Interim data reviewed by an external DSMC is reported. No increment in OS (120 deaths on GC + PF-676, 118 on GC [HR 0.978, 95 % CI 0.74, 1.29]) or PFS (Median 4.9 mos on GC+PF-676, 5.1 mos on GC) was noted for addition of PF-676. Many pts in the PF-676 arm experienced mild/moderate injection site reactions (62% [8 % G3/4]) or flu-like symptoms (37% [4% G3/4]). G3/4/5 thrombocytopenia and neutropenia and transfusions were reported more commonly in pts receiving PF-676 (61% vs 33%, 69% vs 47%, 19% vs 10%). The DSMC recommended termination of the trial due to lack of incremental efficacy and added toxicity. PF-676 administration was discontinued in all pts but collection of follow-up data continues. Updated results will be reported. Conclusions: Addition of PF-676 to GC did not improve the outcome of pts with advanced NSCLC. Alternative development opportunities are being explored for TLR9 agonists in the treatment of cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer