Phase I trial evaluating the epidermal growth factor receptor inhibitor erlotinib in combination with the SRC kinase inhibitor dasatinib for patients with recurrent non-small cell lung cancer (NSCLC)

Abstract

14605 Background: Erlotinib (E), an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK), can prolong survival in patients with advanced NSCLC. SRC TK proteins can cooperate with EGFR and can affect tumor growth, survival, invasion and angiogenesis. For these reasons, we performed a phase I trial investigating E and dasatinib (D), an oral SRC/multi-target TK inhibitor in patients with advanced NSCLC. Methods: Key eligibility criteria included Stage IIIB/IV NSCLC, >1 previous systemic therapies, RECIST measurable disease, ECOG PS 0–1, no prior exposure to EGFR targeting agents. Schema: E PO qD starting day 1, E pharmacokinetics (PK) analysis day 8/9, D PO BID starting day 9, E and D PK analysis day 15. Toxicity evaluation occurred every 7 days for weeks 1–4 (cycle 1) and response evaluation occurred on day 50 ±7. Dose limiting toxicities were recorded during cycle 1. Cohort 1: E 100 D50; Cohort 2: E150 D50; Cohort 3: E150 D70. Results: To date 9 patients (2 M, 7 F) have been enrolled (3, 3, 3) across cohorts 1–3. The average duration of treatment is 62 days. The main adverse events include skin rash (6 grade 1/2, 0 grade 3/4), diarrhea (3 grade 1/2, 0 grade 3/4), and pleural effusions (6 grade 1/2, 0 grade 3/4). Of 8 patients eligible for efficacy, there were no CR/PR, 5 SD, and 3 PD. The administration of escalating doses of D appears to have no affect on the pharmacokinetics of E. Conclusions: The combination of E 150 mg PO qD and D 70 mg PO BID appears to be tolerable with side effects consistent with the two agents (rash and pleural effusions). Additional patients are being examined on this schedule for tolerability and a second cohort of E 150 mg PO qD and D 140 mg PO qD will be explored in an attempt to minimize pleural effusions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Bristol-Myers Squibb