Combined Durvalumab/Gefitinib Combo Shows Promise in EGFR-Mutated NSCLC

Don L. Gibbons, MD, PhD

The first analysis of a trial investigating durvalumab in combination with gefitinib (Iressa) showed encouraging anti-tumor activity and tolerability in patients with non—small cell lung cancer (NSCLC) and EGFR mutations that were tyrosine-kinase inhibitor (TKI)-naïve, according to findings presented at the 2016 European Lung Cancer Conference.

Data were evaluable for 19 patients receiving 2 treatment regimens; 9 patients in arm 1 received concurrent durvalumab and gefitinib and 10 patients in arm 2 received sequential pretreatment with gefitinib followed by the durvalumab/gefitinib combination.

Efficacy was assessed at ≥8 weeks and showed that the investigator-determined best objective response rate (ORR) in arm 1 was 77.8% and 80.0% in arm 2. One (11.1%) patient in arm 1 achieved complete response. Partial response was achieved in 6 (66.7%) and 8 (80.0%) patients in arms 1 and 2, respectively.

Stable disease >8 weeks was observed in 2 (22.2%) and 1 (10.0%) patient in arms 1 and 2, respectively. Stable disease lasting >24 weeks was demonstrated by 1 patient (10%) in arm 2.

“Reduction in tumor size was observed in all patients treated with gefitinib and durvalumab,” said Don L. Gibbons, MD, PhD, assistant professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “Durvalumab is a human IgG1 monoclonal antibody that selectively blocks interaction of programmed death ligand-1 (PD-L1) with PD-1 and CD-80. By combining durvalumab with gefitinib, we were looking to attain a more durable response and to delay the development of resistance to gefitinib.”

Gibbons reported preliminary results from an ongoing dose-expansion phase of a phase I open-label multicenter study evaluating the safety and tolerability of the combined therapy of durvalumab plus gefitinib. Enrolled patients are TKI-naïve with NSCLC and sensitizing EGFR mutations; 11 patients had exon 19 deletion and 8 patients harbored exon 21 L858R mutations.

The ongoing trial is recruiting patients; however, in this analysis the treatment arms have 10 patients each. Patients in arm 1 receive concurrent durvalumab at 10 mg/kg every 2 weeks plus gefitinib at 250 mg once daily, while patients in arm 2 received 4 weeks of gefitinib monotherapy followed by durvalumab plus gefitinib at the same dose as arm 1. Patient characteristics were balanced across both arms.

The trial’s primary endpoints were safety and tolerability; secondary endpoints included tumor response by RECIST 1.1, pharmacokinetics, pharmacodynamics, and immunogenicity.

Biopsies were taken at baseline and at treatment evaluation for determination of PD-L1 expression; at baseline, only 3 (17%) patients had PD-L1 expression greater than 25%.

At data cut-off, follow-up was ≥3 months for all patients. Results showed that the primary endpoints were met and that the gefitinib/durvalumab combination was tolerable in most patients.

The most frequently reported treatment-related grade 3/4 adverse events (AEs) in both arms were increased ALT (70% arm 1, 60% arm 2) and increased AST (40% arm 1, 50% arm 2). No significant pharmacokinetics or pharmacodynamics interactions were observed.

“These results support potential future investigation of combined durvalumab/gefitinib treatment in NSCLC,” Gibbons concluded.

Gibbons DL, Chow LQ, Kim DW, 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. Presented at: 2016 European Lung Cancer Conference; April 13-16, 2016; Geneva, Switzerland. Abstract 570.

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