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
Mené sur 56 patients atteints d’un cancer du poumon non à petites cellules EGFR+ de stade localement avancé ou métastatique, cet essai de phase I évalue la dose maximale tolérée et l’efficacité, du point de vue du taux de réponse objective, du durvalumab en combinaison avec le géfitinib, et analyse les caractéristiques pharmacocinétiques de cette combinaison
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.