Venclexta (venetoclax) plus Gazyva (obinutuzumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved May 2019

Specific Treatments:

chronic lymphocytic leukemia or small lymphocytic lymphoma

Therapeutic Areas

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General Information

Venclexta (venetoclax) is a is a BCL-2 inhibitor. Gazyva (obinutuzumab) is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells.

Venclexta (venetoclax) plus Gazyva (obinutuzumab) is specifically indicated for treatment of people with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Venclexta in combination with obinutuzumab is supplied as a tablet for oral administration. The recommended dose is as follows: Start obinutuzumab administration at 100 mg on Cycle 1 Day 1, followed by 900 mg on Cycle 1 Day 2. Administer 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of each subsequent 28 day cycle, for a total of 6 cycles. Refer to the obinutuzumab prescribing information for recommended obinutuzumab dosing information. On Cycle 1 Day 22, start Venclexta according to the 5-week ramp-up schedule on the drug label. After completing the ramp-up schedule on Cycle 2 Day 28, patients should continue Venclexta 400 mg once daily from Cycle 3 Day 1 until the last day of Cycle 12.

Clinical Results

FDA Approval

The FDA approval of the Gazyva Venclexta combination was based on results of the randomized Phase III CLL14 study. The trial enrolled 432 patients with previously untreated CLL who were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). Arm A started with an initial cycle of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce tumor burden. The primary endpoint of the study was investigator-assessed progression-free survival (PFS). Results showed the combination of Venclexta plus Gazyva produced a durable and significant reduction in the risk of disease worsening or death (progression-free survival (PFS), as assessed by Independent Review Committee) by 67 percent compared to Gazyva plus chlorambucil, a current standard of care. Venclexta plus Gazyva showed deep and clinically meaningful responses characterized by a higher rate of minimal residual disease (MRD)-negativity in the bone marrow compared to Gazyva plus chlorambucil (MRD-negativity of 57 percent vs. 17 percent) and peripheral blood (MRD-negativity of 76 percent vs. 35 percent).

Side Effects

Adverse effects associated with the use of Venclexta plus Gazyva may include, but are not limited to, the following:

low white blood cell count

diarrhea

fatigue

nausea

low red blood cell count

upper respiratory tract infection

Mechanism of Action

Venclexta (venetoclax) is a is a BCL-2 inhibitor. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis. Gazyva (obinutuzumab) is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body's immune system.

Additional Information

For additional information regarding Gazyva plus Venclexta or chronic lymphocytic leukemia or small lymphocytic lymphoma, please visit the Venclexta page