Small cell lung cancer (SCLC) is a chemoresponsive malignancy with high response rates in early lines of therapy, but will inevitably recur. For patients (pts) with progressive SCLC following treatment with at least two prior therapies, standard treatment has not been established. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate that targets Delta-like protein 3 (DLL3), an atypical Notch receptor family ligand and a marker specific for tumor-initiating cells in SCLC and other neuroendocrine cancers. Rova-T is comprised of a humanized DLL3-specific IgG1 monoclonal antibody tethered to a toxic DNA cross-linking agent by a cleavable linker. Rova-T binds DLL3 on target-expressing cells, is internalized, and the toxin released to induce cell death. A Phase 1 study of Rova-T in SCLC demonstrated robust antitumor activity in DLL3-high pts and a manageable safety profile1. The safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of Rova-T has not been evaluated in Japanese SCLC pts, thus a study of Rova-T in this population is warranted.
This is a Phase 1, multicenter, Japanese, open-label dose escalation study (NCT03086239). Primary objective: to assess safety and tolerability of Rova-T in Japanese pts with advanced, recurrent SCLC. Secondary objectives: to explore antitumor activity of Rova-T; to study PK and pharmacodynamics of Rova-T. Pt eligibility: histologically or cytologically confirmed advanced, recurrent SCLC with measurable disease and documented disease progression after at least 2 prior systemic regimens, including at least 1 platinum-based regimen; ECOG 0-1; no prior exposure to a pyrrolobenzodiazepine-based drug. A standard 3 + 3 dose escalation will be used with ≤ 18 pts enrolled (6/dose level x 3 levels) and ≤ 60 pts if expansion cohorts are executed (20/dose level x 3 levels). Pts will receive Rova-T 0.2, 0.3, or 0.4 mg/kg intravenously on Day 1 of each 6-week cycle x 2 doses and dexamethasone 8 mg orally twice daily on Day -1, Day 1, and Day 2 of each 6-week cycle. Dose escalation will proceed until a single maximum tolerated dose (MTD) is determined (not to exceed 0.4 mg/kg). 1. Rudin et al., Lancet Oncol, 2016.
Clinical trial identification
Legal entity responsible for the study
I. Okamoto, H. Udagawa, S. Kanda, M. Takeda, H. Akamatsu: Serves as an investigator for Abbvie Stemcentrx. T.H. Han, I. Lakatos, F. Zhang, C. Scripture: Employee of AbbVie Stemcentrx and may own AbbVie stock. S. Okubo: Employee of AbbVie and may own AbbVie stock. All other authors have declared no conflicts of interest.