Durvalumab 10 mg/kg plus gefitinib 250 mg demonstrated encouraging activity with favorable tolerability in tyrosine kinase inhibitor (TKI)-naïve patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), a study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1
Durvalumab, a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, blocks the interaction among PD-L1, PD-1, and CD80 with high affinity and selectivity. In this phase 1 expansion study, researchers sought to evaluate the efficacy, safety, and tolerability of durvalumab combined with gefitinib in patients with EGFR mutation-positive NSCLC who have not previously received a TKI.
Researchers enrolled 20 to the expansion portion. Half received durvalumab 10 mg/kg intravenously every 2 weeks plus gefitinib 250 mg orally once daily (arm 1), while the other 10 patients received gefitinib monotherapy followed by concurrent durvalumab plus gefitinib (arm 2).
Results showed that the best objective response rate was 77.8% in arm 1 and 80.0% in arm 2. One patient in arm 1 achieved a complete response while the others had partial responses. Stable disease lasting for 8 weeks or more occurred in 2 and 1 patients in arm 1 and arm 2, respectively.
In regard to safety, 4 patients in arm 2 discontinued treatment due to grade 3 or 4 adverse events, including 3 cases of elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and 1 case of pneumonitis. The most frequently reported adverse events included diarrhea, ALT elevation, rash, AST elevation, pruritus, nausea, and dry skin.
The findings ultimately support further evaluation of investigational durvalumab in combination with gefitinib in this patient population.
- Gibbons DL, Chow LQ, Kim D, et al. Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): a phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC. Oral presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.