Tg01, A New Potent Cox-2 Inhibitor In Combination With Erlotinib In Metastatic Or Recurrent Non-Small Cell Lung Cancer (Nsclc) Patients: A Phase 1 Study

14661 Background: TG01 is an oral, potent and selective inhibitor of COX-2. The COX-2 pathway plays a key role in tumor dependent angiogenesis and growth. Preclinical studies of TG01 show in vitro and in vivo activity in xenograft models. Thus, TG01 is being studied in advanced solid tumors. COX-2 signaling activates the Erk/MAPK pathway (Krysan et al Cancer Res 2005; 65:6275) thus combinations of COX-2 and EGFR inhibitors are of interest, particularly in advanced NSCLC. The purpose of this study was to determine the safety and feasibility of TG01 in combination with the EGFR-TKI, erlotinib in NSCLC patients. Methods: Patients with recurrent or metastatic NSCLC were treated with erlotinib (150 mg PO daily) and escalating doses of TG01 (100 - 1200 PO daily). Prior treatment with an EGFR TKI was allowed. PK for TG01 and erlotinib will be evaluated. PGE-M a urinary metabolite of PGE2 will be collected at baseline and Day 15 of C1 and Day 1 of C2. The recommended phase II dose will be based on ≥ 75% inhibition of PGE-M and/or the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) is defined as drug related G3 and G4 events. Results: Six patients have been enrolled (3 at TG01 100mg; 3 at TG01 200mg). Characteristics: Sex: 4 F; Age range 57–80; ECOG PS 0 or 1 (0=3, 1=3). Number of prior therapies: 2–5. There have been no DLTs; most common adverse events include G1 and G2 nausea, diarrhea and rash (2 pts each). Of three evaluable patients: 1 PR, 2 SD. TG01 pharmacokinetics reveal a median Tmax of 2 hours (range 1.5–4), mean (SD) T1/2 of 11.8 (5.3) hours, Cmax of 313.0 (99.6) ng/ml and AUC (0-t) of 2816 (1204) ng.h/ml. Conclusions: 1) TG01 and erlotinib have been safely administered in doses evaluated to date. Accrual to additional cohorts is ongoing. 2) PGE-M analysis of the 1st 2 cohorts is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Pharmaceuticals, Tragara Pharmaceuticals Inc. Tragara Pharmaceuticals Inc.