Rovalpituzumab Tesirine as a Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From the Phase 3 MERU Study

ABSTRACT Introduction Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like protein 3 (DLL3), an atypical Notch ligand expressed in small cell lung cancer (SCLC) tumors. We evaluated the efficacy of Rova-T versus placebo as maintenance therapy in patients with extensive stage (ES) SCLC after platinum-based chemotherapy. Methods MERU was a phase 3 randomized, double-blinded, placebo-controlled study. Patients without disease progression following 4 cycles of platinum-based front-line chemotherapy were randomized in a 1:1 ratio to receive 0.3 mg/kg Rova-T or placebo (q6wk, omitted every third cycle). Primary efficacy endpoints were progression-free survival (PFS) assessed by the Central Radiographic Assessment Committee (CRAC) and overall survival (OS) in DLL3-high patients. Results Median age of all randomized patients (N=748) was 64 years; 78% had TNM stage IV disease. At futility analysis of the DLL3-high subset, the hazard ratio (HR) for OS was 1.07 (95% CI: 0.84-1.36) favoring placebo arm, with median OS of 8.5 and 9.8 months in the Rova-T and placebo arms, respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.0 versus 1.4 months, HR=0.48; P Conclusions Due to the lack of survival benefit in the Rova-T arm, the study did not meet its primary endpoint and was terminated early. As a result, CRAC assessment of PFS was not performed. The frequency of Grade ≥3 and drug-related toxicities were higher with Rova-T vs placebo. Rova-T was associated with unique toxicities such as pleural and pericardial effusions, photosensitivity reaction, and peripheral edema, which should be carefully considered in the ES SCLC population.