Details

Autor(en) / Beteiligte

• Creelan, Benjamin C
• 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

Titel

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

Ist Teil von

• British journal of cancer, 2021-01, Vol.124 (2), p.383-390

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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). 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.