Verastem Oncology has dosed the first patient in its Phase 1/2 trial testing a combination of duvelisib and Venclexta (venetoclax) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who failed prior therapies.
The open-label trial (NCT03534323), which is still recruiting, is being conducted at the Dana-Farber/Harvard Cancer Center in Boston and is expected to include 47 adults. For more information on patient enrollment, click here.
“We are excited to conduct this trial, as these new, targeted agents in development have the potential to improve patients’ response through combination therapies,” Matthew Davids, MD, assistant professor of medicine at Harvard Medical School and principal investigator of the trial, said in a press release.
“Duvelisib and venetoclax target different pathways fundamental to CLL biology and have distinct mechanisms of action,” said Davids, who is also the associate director of the Center for Chronic Lymphocytic Leukemia at the Dana-Farber Cancer Institute. “We now have the opportunity to explore whether this combination may be an effective therapy for the treatment of patients with CLL.”
Duvelisib, formerly known as IPI-145, is an investigational small molecule inhibitor that blocks the activity of two enzymes — called PI3K-delta and PI3K-gamma — known to support the growth and survival of malignant B- and T-cells.
In relapsed or refractory CLL/SLL patients, duvelisib extended the time to disease progression or death, compared with standard Arzerra (ofatumumab), results from the Phase 3 DUO trial (NCT02004522) showed. It also showed high response rates in the Phase 2 DYNAMO trial for indolent (or slow-growing) non-Hodgkin’s lymphoma (NHL).
This led Verastem to submit an application with the U.S. Food and Drug Administration requesting duvelisib’s full approval for relapsed or refractory CLL/SLL patients and an accelerated approval for relapsed or refractory follicular lymphoma. The FDA granted priority review to the submission, and a decision is expected by Oct. 5.
Venclexta is a potent inhibitor of the BCL-2 protein, a protein that prevents cell death. It is approved in the U.S. for CLL patients with a particular genetic mutation — the 17p deletion — who have failed at least one prior therapy.
In the trial, researchers first intend to determine the dose of Venclexta that is safe to give in combination with duvelisib. They also aim to study the side effects of this combination.
In the Phase 2 part, researchers will then study the effectiveness of the combination, including response rate, complete response rate, duration of response, time to disease progression or death, and the rate of patients who achieve minimal residual disease negativity — lack of cancer cells in blood and bone marrow.
“As we continue to explore the potential of duvelisib, we are very encouraged by the strong scientific rationale and the preclinical data supporting the combination of duvelisib and venetoclax,” said Diep Le, MD, PhD, chief medical officer of Verastem Oncology. “We expect this trial will help enhance our understanding of the effects of this combination in the treatment of patients with CLL/SLL.”
Verastem is also studying duvelisib, alone (NCT03372057) or in combination treatments (NCT02783625), in peripheral T-cell lymphoma patients. Both studies are recruiting participants. For additional information, follow the links above.