First-in-Class Rovalpituzumab Tesirine Active in Recurrent Small Cell Lung Cancer


Key Points

  • Rovalpituzumab tesirine is a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3).
  • In patients with recurrent small cell lung cancer, responses to this agent were more frequent in patients with elevated DLL3 expression.

In a phase I study reported in The Lancet Oncology, Rudin et al found that rovalpituzumab tesirine, a first-in-class antibody-drug conjugate directed against delta-like protein 3 (DLL3), produced responses in patients with recurrent small cell lung cancer (SCLC). DLL3 is a target identified in tumor-initiating cells that has been found to be expressed in > 80% of patients with SCLC.

Study Details and Toxicity

The study included 74 patients with SCLC previously treated with one or two chemotherapy regimens, including a platinum-based regimen. Dose-escalation or -expansion cohorts received doses of 0.05 mg/kg to 0.8 mg/kg given intravenously every 3 or 6 weeks, followed by investigation of 0.3 and 0.4 mg/kg every 6 weeks and 0.2 mg/kg every 3 weeks.

Dose-limiting toxicity was observed at 0.8 mg/kg every 3 weeks, including grade 4 thrombocytopenia in 2 patients and grade 4 liver function test abnormalities in 1 patient. The most common grade ≥ 3 treatment-related adverse events were thrombocytopenia (11%), pleural effusion (8%), and increased lipase (7%). Drug-related serious adverse events occurred in 38%. The maximum tolerated dose was 0.4 mg/kg every 3 weeks, with the dose of 0.3 mg/kg every 6 weeks moving forward into phase II study.

Antitumor Activity

At active doses, consisting of 0.2 or 0.4 mg/kg every 3 weeks or 0.3 or 0.4 mg/kg every 6 weeks, objective response was observed in 11 of 60 assessable patients (18%), including in 10 of 26 (38%) with confirmed high DLL3 expression.

The investigators concluded: “Rovalpituzumab tesirine shows encouraging single-agent antitumour activity with a manageable safety profile. Further development of rovalpituzumab tesirine in DLL3-expressing malignant diseases is warranted.”

The study was funded by Stemcentrx Inc.

Charles M. Rudin, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.