Rovalpituzumab tesirine demonstrated encouraging single-agent antitumor activity with a manageable toxicity profile among patients with recurrent small cell lung cancer (SCLC), according to a study published in The Lancet Oncology.1

Delta-like protein 3 (DLL3) is a novel target identified in tumor-initiating cells, and is expressed in more than 80% of patients with SCLC. Researchers evaluated the activity and safety of rovalpituzumab tesirine, a first-in-class antibody-drug conjugate directed against DLL3, among patients whose disease progressed after 1 or more prior regimens.

For the open-label, phase 1 study ( Identifier: NCT01901653), researchers enrolled 82 patients with SCLC or large-cell neuroendocrine tumors with progressive disease who previously received 1 to 2 previous regimens, including a platinum-based regimen. Participants received rovalpituzumab tesirine at varying doses every 3 weeks or every 6 weeks.

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Dose-limiting toxicities occurred at a dose of 0.8 mg/kg every 3 weeks, including grade 4 thrombocytopenia in the 2 patients that received that dose level and grade 4 liver function test abnormalities in 1 patient. The most common grade 3 or worse treatment-related adverse events in the 74 patients with SCLC were thrombocytopenia (11%), pleural effusion (8%), and increased lipase (7%).

Among those with SCLC, 38% experienced treatment-related serious adverse events.

Eighteen percent of the evaluable 60 patients achieved a confirmed objective response, with a median duration of 5.6 months (95% CI, 2.5-8.3). Thirty-eight percent of 26 patients with confirmed high DLL3 expression achieved a response with a median duration of 4.3 months (95% CI, 2.2-15).

Median progression-free survival was 2.8 months (95% CI, 2.5-4.0) and 4.3 months (95% CI, 2.8-5.6) overall and for patients with high DLL3 expression, respectively.

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The findings suggest that further assessment of rovalpituzumab tesirine in DLL3-expressing malignant diseases is warranted.


  1. Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2016 Dec 5. doi: 10.1016/S1470-2045(16)30565-4 [Epub ahead of print]