Gefitinib plus tremelimumab combination in refractory non-small cell lung cancer patients harbouring EGFR mutations: the GEFTREM phase I trial
Mené sur 27 patients atteints d'un cancer du poumon non à petites cellules présentant des mutations EGFR, réfractaire aux inhibiteurs de tyrosine kinase anti-EGFR de première génération et de stade avancé, cet essai de phase I évalue la dose maximale tolérée du trémélimumab en combinaison avec le géfitinib
Introduction : A phase I open-label multicentre study was initiated to evaluate the association oftremelimumab with gefitinib in EGFR-mutant NSCLC patients who progressed after first-generation EGFR-TKI. Here we provide the efficacy data from the entire cohort. Material and methods : Patients with advanced EGFR-mutant NSCLC with progression after response to EGFR-TKIwere enrolled. Study treatment was gefitinib 250 mg daily and tremelimumab at 3 doselevels: 3, 6 and 10 mg/kg IV Q4W for 6 cycles followed by Q12W until progression orunacceptable toxicity. The primary objective was safety and tolerability, and to establisha RP2D. Results : Between January 2014 and July 2015, 27 patients (21 in the escalating dose cohortand 6 in expansion cohort) received at least one dose of tremelimumab. DLTs occurredin 4 patients: 1 at 3mg/kg (one grade 3 diarrhoea), 1 at 6mg/kg (one grade 3 diarrhoea)and 2 at 10mg/kg (one grade 3 diarrhoea and one grade 3 AST/ALT increase) of tremelimumab. Grade 3 TRAE occurred in 22 patients (81%), most frequently diarrhoea (30%) and ALT/ASTincrease (15%). Stable disease was the best overall response in 72% patients, withmedian PFS of 2.2 months (95% CI, 1.8-4.2). All patients discontinued treatment, mostfrequently due to disease progression (63% of patients). Conclusion : The recommended dose of tremelimumab in combination with gefitinib in EGFR-mutant NSCLC patients was 3mg/kg. The gastrointestinal toxicity and the limited efficacydata prevented further evaluation of this combination. (GEFTREM; clinical trial numberNCT02040064)