A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer
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Published:2020-10-05
Issue:2
Volume:124
Page:383-390
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ISSN:0007-0920
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Container-title:British Journal of Cancer
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language:en
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Short-container-title:Br J Cancer
Author:
Creelan Benjamin C.ORCID, Yeh Tammie C., Kim Sang-We, Nogami Naoyuki, Kim Dong-Wan, Chow Laura Q. M., Kanda Shintaro, Taylor Rosemary, Tang Weifeng, Tang Mei, Angell Helen K., Roudier Martine P., Marotti Marcelo, Gibbons Don L.ORCID
Abstract
Abstract
Background
EGFR tyrosine kinase inhibitors (TKIs) induce cytolysis and release of tumour proteins, which can stimulate antigen-specific T cells. The safety and efficacy of durvalumab and gefitinib in combination for TKI-naive patients with advanced EGFRm NSCLC was evaluated.
Methods
This Phase 1 open-label, multicentre trial (NCT02088112) was conducted in 56 patients with NSCLC. Dose expansion permitted TKI-naive patients, primarily with activating L858R or Ex19del EGFRm. Arms 1 + 1a received concurrent therapy; Arm 2 received 4 weeks of gefitinib induction followed by concurrent therapy.
Results
From dose escalation, the recommended dose of durvalumab was 10 mg/kg Q2W with 250 mg QD gefitinib. Pharmacokinetics were as expected, consistent with inhibition of soluble PD-L1 and no treatment-emergent immunogenicity. In dose expansion, 35% of patients had elevated liver enzymes leading to drug discontinuation. In Arms 1 + 1a, objective response rate was 63.3% (95% CI: 43.9–80.1), median progression-free survival (PFS) was 10.1 months (95% CI: 5.5–15.2) and median response duration was 9.2 months (95% CI: 3.7–14.0).
Conclusions
Durvalumab and gefitinib in combination had higher toxicity than either agent alone. No significant increase in PFS was detected compared with historical controls. Therefore, concurrent PD-L1 inhibitors with gefitinib should be generally avoided in TKI-naive patients with EGFRm NSCLC.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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