Results from a phase 1b study of telisotuzumab vedotin in combination with osimertinib in patients with c-Met protein–overexpressing, EGFR-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) after progression on prior osimertinib
Mené sur 38 patients atteints d'un cancer du poumon non à petites cellules (métastatique ou de stade localement avancé) avec mutation EGFR et surexpression de la protéine c-Met (durée médiane de suivi : 7,4 mois), cet essai multicentrique de phase 1b évalue la tolérabilité et la toxicité de l'ajout du télisotuzumab védotin à l'osimertinib après échec de ce dernier pour enrayer la progression tumorale
Résumé en anglais
Background : Osimertinib is the standard first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. However, treatment resistance is inevitable and increased c-Met protein expression correlates with resistance. Telisotuzumab vedotin (Teliso-V) is an antibody-drug conjugate that targets c-Met protein overexpression. Herein, we report the results of a phase 1/1b trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on osimertinib.
Patients and methods : This multicenter, open-label study (NCT02099058) enrolled patients with advanced EGFR-mutated, c-Met protein–overexpressing, non-squamous NSCLC that had progressed on prior osimertinib. Patients received Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily). Teliso-V was evaluated at 1.6 mg/kg in a safety lead-in phase and escalated to 1.9 mg/kg. Dose expansion included both doses. Endpoints included safety and tolerability, pharmacokinetics, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS).
Results : A total of 38 patients received Teliso-V (1.6 mg/kg, n=20; 1.9 mg/kg, n=18) plus osimertinib and were included in this analysis. No dose-limiting toxicities were observed. Most frequent any-grade treatment-emergent adverse events (TEAEs) were peripheral sensory neuropathy (50%), peripheral edema (32%), and nausea (24%). Most common grade 3/4 TEAEs were anemia (11%) and pulmonary embolism (8%). Five TEAEs led to death; none were reported as being related to Teliso-V or osimertinib. The pharmacokinetic profile of Teliso-V plus osimertinib was similar to Teliso-V monotherapy. After a median follow-up of 7.4 months, ORR was 50.0% per independent central review (ICR) (DOR not reached), and median PFS per ICR was 7.4 months (95% CI: 5.4, NR).
Conclusions : Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein–overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.
