Brief Report: A Phase 1 Study Evaluating Rovalpituzumab Tesirine (Rova-T) in Frontline Treatment of Patients With Extensive-Stage Small Cell Lung Cancer
Mené sur 26 patients atteints d'un cancer du poumon à petites cellules de stade étendu (âge médian : 66 ans), cet essai de phase I évalue la dose tolérable du rovalpituzumab tésirine en traitement de première ligne et l'intérêt, du point de vue de l'amélioration de la survie, d'ajouter ce conjugué anticorps-médicament à une chimiothérapie à base de platine
Résumé en anglais
Introduction : Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like protein 3, a Notch pathway ligand highly expressed on small cell lung cancer (SCLC) cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (CE) in frontline treatment of extensive-stage SCLC.
Methods : One cycle of CE pre-enrollment was permitted (later mandated). Four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, q6 weeks ×2; Cohort 1; n=4); Rova-T induction (0.3 mg/kg, q6 weeks ×2) followed by CE q21 ×4 (Cohort 2; n=5); Rova-T (0.1 or 0.2 mg/kg, q6 weeks ×2) overlapping with CE q21 ×4 (Cohort 3; n=14); and Rova-T maintenance (0.3 mg/kg, q6 weeks ×2) after CE q21 ×4 (Cohort 4; n=3).
Results : Twenty-six patients were dosed (Cohort 3: 14; Cohorts 1,2,4 combined: 12). Median age was 66 years, and 73% had ECOG 1. In Cohort 3, 7 (50%) patients had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with Cohorts 1,2,4 combined, Cohort 3 showed lower frequency of some Rova-T–related adverse events of special interest (AESI) such as pleural effusion (0 vs 33%), pericardial effusion (0 vs 17%), ascites (0 vs 8%), peripheral edema (36% vs 42%), generalized edema (0 vs 8%), pneumonia (7% vs 25%), and hypoalbuminemia (0 vs 17%).
Conclusions : Lower Rova-T doses may be associated with lower incidence of some Rova-T–related AESI. Rova-T 0.2 mg/kg + CE (Cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE.
