by Dr. C.H. Weaver M.D. updated 8/2019
The developer of Rovalpituzumab tesirine (Rova-T) halted the key clinical trial in August 2019 because Rova-T failed to meet the trial endpoint demonstrating effectiveness in SCLC. Rova-it is an antibody-drug conjugate that targets a protein associated with the small cell lung cancer cells and is the first biomarker-directed treatment being developed in SCLC. In SCLC, a proportion of the malignant cells display Delta-like protein 3 (DLL3) which is not seen on the surface of normal cells. Rova-T is a combination of an antibody that binds to DLL3 that delivers a toxic substance called tesirine directly to the cancer cells.(1,2)
SCLC is an aggressive and fast-growing type of cancer that is very responsive to chemotherapy. However, although initial anticancer responses to chemotherapy may be substantial, long-term survival for patients with SCLC remains poor. Survival in SCLC is no more than 15%, 2 years after diagnosis. These statistics haven’t changed in 40 years and only one drug has been approved to treat recurrent disease.
The results of a clinical trial evaluating 74 patients with SCLC who had failed at least one previous line of therapy were reported at the American Society of Clinical Oncology cancer research meetings in Chicago and initially appeared promising.(2)
Overall 18% of these refractory patients had a confirmed response regardless of the level of DLL3 expression, and the rate among those who were DLL3-high was 39%. A confirmed clinical benefit rate defined as stable disease or better was achieved in 89% of patients who were DLL3-high expressers.
Rova-T will be undergoing additional evaluation in clinical trials alone and in combination with other chemotherapy drugs in the near future.
- Rudin CM, Pietanza M, Bauer T, et al. Safety and efﬁcacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC). J Clin Oncol 34, 2016 (suppl; abstr LBA8505). Can be accessed at: http://abstracts.asco.org/176/AbstView_176_162941.html