‘Clinically Meaningful’ Response Achieved With Venetoclax for 17p-Deletion CLL

For patients with relapsed or refractory CLL who harbor the 17p deletion, venetoclax may offer a new treatment option.

Venetoclax (ABT-199) met the primary endpoint in a phase II trial, achieving improved overall response rates in a difficult-to-treat form of chronic lymphocytic leukemia (CLL), Genentech announced Wednesday.

The pivotal open-label, single-arm clinical efficacy and safety phase II M13-982 international trial (NCT01889186) showed that monotherapy with the oral B-cell lymphoma-2 (BCL-2) inhibitor venetoclax demonstrated “a clinically meaningful reduction in the number of cancer cells” among patients with relapsed or refractory CLL, whose cancer cells harbor the 17p deletion, according to the Genentech announcement.

“Approximately 30% to 50% of people with relapsed or refractory chronic lymphocytic leukemia have the 17p deletion that makes their disease difficult to treat,” noted Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech.

The study has enrolled 107 patients. No unexpected safety signals were reported.

Genentech and AbbVie have partnered to develop venetoclax, an investigational oral small-molecule selective inhibitor of the BCL-2 protein. BCL-2 inhibits apoptosis in lymphocytes and is overexpressed in CLL, non-Hodgkin lymphoma, and other B-cell malignancies.

“Venetoclax may help restore the natural process that allows these [17p-deletion-harboring] leukemic cells to self-destruct, representing a potential new way of helping people with this form of CLL, who typically have a poor prognosis and limited treatment options,” Horning said.

CLL is the most common form of blood cancer, representing approximately 25% of newly-diagnosed leukemia cases each year in the United States. At the time of diagnosis, between 3% and 10% of patients with CLL harbor the 17p deletion.

Regulatory applications based on the phase II trial results will be submitted to the US Food and Drug Administration (FDA) and European Medicines Agency by the end of 2015, Genentech announced. Venetoclax was granted fast-track FDA Breakthrough Therapy Designation in May 2015 for treatment of CLL.