FDA Approves Venclexta-Gazyva Combo for Untreated CLL/SLL Patients

The U.S. Food and Drug Administration (FDA) has approved the double combination therapy of Venclexta (venetoclax) and Gazyva (obinutuzumab) for the treatment of adults with newly diagnosed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Venclexta is a potent selective inhibitor of the B-cell lymphoma-2 (BCL-2) protein that works by preventing cancer cells from over-producing this protein, priming them for programmed cell death. It is being developed and marketed by Genentech and AbbVie.

Gazyva is a monoclonal antibody that has been designed to bind CD20, a protein found on the surface of B cells, including malignant CLL/SLL cells, destroying them. It is also being marketed by Genentech, a subsidiary of Roche.

After granting Priority Review and the designation of Breakthrough Therapy to Venclexta in combination with Gazyva for the treatment of untreated CLL patients, the FDA has now approved it as a first-line treatment for patients with CLL or SLL. The prescribing information can be found here.

“Venclexta plus Gazyva is the only chemotherapy-free option of fixed duration that provides durable responses to help people live longer without progression of their disease, compared to a standard of care,” Genentech’s Sandra Horning, MD, chief medical officer and head of global product development, said in a press release.

“Today’s approval represents our longstanding commitment to helping people with blood cancers throughout the course of their disease, and we are excited to provide this new option for untreated chronic lymphocytic leukemia,” she said.

The approval was based on data from the prospective, multicenter, randomized, open-label, CLL14 Phase 3 trial (NCT02242942), whose findings will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 31-June 4 in Chicago.

The study was designed to assess the safety and efficacy of the fixed-duration combination of Venclexta plus Gazyva compared to Gazyva plus chlorambucil in a group of CLL untreated patients.

The trial enrolled 432 patients who were randomly assigned to receive either one year of treatment with Venclexta together with six months of therapy with Gazyva, or a six-month treatment with Gazyva plus chlorambucil, followed by an additional six months of chlorambucil.

The trial’s primary endpoint was to assess progression-free survival (the time patients lived without their disease worsening). Secondary endpoints included treatment safety assessments, minimal residual disease (MRD, very low number of cancer cells remaining after treatment) status, overall response, overall survival, and duration of response.

Results showed that patients receiving the double combination of Venclexta and Gazyva had a reduction of approximately 67% in the risk of disease progression or death, compared to those treated with Gazyva plus chlorambucil.

In addition, patients treated with Venclexta and Gazyva had a significantly higher percentage of MRD negativity in bone marrow and peripheral blood samples — 57% versus 17% for bone marrow; and 76% versus 35% for peripheral blood.

A tissue or blood sample is considered MRD-negative when less than one malignant cancer cell is detected among 10,000 white blood cells.

The most common adverse events associated with Venclexta plus Gazyva included low white blood cell counts, diarrhea, fatigue, nausea, low red blood cell counts, and upper respiratory tract infections.

Additional regulatory submissions based on data from the CLL14 trial to other health authorities worldwide are underway.