A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC

IntroductionRovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin carboplatin combined etoposide [CE]) frontline treatment of extensive-stage SCLC.MethodsOne cycle CE pre-enrollment permitted (later mandated). The following four cohorts were enrolled: monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); induction q6 2) followed by 21 days (q21) 4 (cohort 5); (0.1 0.2 overlapping q21 3; 14); and maintenance after 4; 3).ResultsA total 26 patients dosed 3: 14; 1, 2, combined: 12). Median age 66 years, 73% had Eastern Cooperative Oncology Group performance status 1. In 3, seven (50%) confirmed objective responses, median progression-free survival 5.2 months overall 10.3 months. Compared combined, 3 lower frequency some Rova-T–related adverse events special interest, such as pleural effusion (0 versus 33%), pericardial 17%), ascites 8%), peripheral edema (36% 42%), generalized pneumonia (7% 25%), hypoalbuminemia 17%).ConclusionsLower doses may be associated incidence interest. mg/kg plus 3) tolerable; however, there no clear efficacy benefit adding to CE.