1537TiP - A Phase 3 Trial of Rovalpituzumab Tesirine vs Topotecan in Patients with Advanced Small Cell Lung Cancer Following Frontline Platinum-Based Chemoth...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Philip Komarnitsky
Citation Annals of Oncology (2017) 28 (suppl_5): v539-v542. 10.1093/annonc/mdx386
Authors P. Komarnitsky1, H. Lee2, M. Shah2, S. Wong2, S. Gulbranson2, J. Dziubinski2, L. Caffrey2, P. Tanwani2, M. Motwani2, F. Zhang2
  • 1Oncology Development, AbbVie Inc., 02139 - Cambridge/US
  • 2Clinical Development, AbbVie Inc., North Chicago/US

Abstract

Background

Small cell lung cancer (SCLC) represents ∼15% of lung cancers. Patients (pts) are staged with limited or extensive stage disease (ES). ES standard therapy consists of a platinum-based therapy + a second agent (etoposide). Initial response rates are high but not durable. Treatment for relapsed pts is limited, but includes topotecan. However, efficacy of topotecan is suboptimal and there is a high unmet need in this population. Delta-like protein 3 (DLL3) is an atypical Notch receptor family ligand identified as a target in SCLC and neuroendocrine carcinomas (NECs). DLL3 is highly expressed in SCLC and NECs but not normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a toxic DNA crosslinker. Rova-T has antitumor activity in relapsed ES SCLC pts, and was well-tolerated1. Thus, we are investigating Rova-T vs topotecan as a 2nd line therapy in advanced SCLC.

Trial design

This is a Phase 3, randomized, open-label, multicenter study (NCT03061812) to assess efficacy, safety, and tolerability of Rova-T vs topotecan. Approximately 411 pts will be enrolled and randomized 2:1 between 2 arms. Arm A regimen: 0.3 mg/kg Rova-T intravenous (IV) on Day 1 + 8 mg dexamethasone orally, twice daily on Day -1, 1 and 2 of a 42-day cycle; administered for 2 cycles with up to 2 additional cycles permitted. Arm B: 1.5 mg/m2 topotecan (or per local label) IV on Days 1-5 of each 21-day cycle; administered until disease progression. Pt eligibility: ≥ 18 years; confirmed, advanced/metastatic SCLC with first disease progression following frontline standard therapy; DLL3-high tumor expression; ECOG 0-1; no prior exposure to a pyrrolobenzodiazepine-based drug or topotecan, irinotecan, or other topoisomerase I inhibitor. Primary objectives: to determine if Rova-T improves objective response rate and overall survival vs topotecan. Secondary objectives: to assess if Rova-T improves progression-free survival vs topotecan; to compare duration of objective response between arms; and to assess effect on patient-reported outcomes. 1. Rudin et al., Lancet Oncol, 2016.

Clinical trial identification

NCT03061812

Legal entity responsible for the study

AbbVie Inc.

Funding

AbbVie Inc.

Disclosure

P. Komarnitsky, H-J. Lee, M. Shah, S. Wong, S. Gulbranson, J. Dziubinski, L. Caffrey, P. Tanwani, M. Motwani, F. Zhang: Employee of AbbVie and may own stock.