New Clinical Data - Venetoclax and Gazyva

Chronic lymphocytic leukemia, like other cancers, represents an uncontrolled growth of cells.

Chronic Lymphocytic Leukemia, or CLL

CLL is a common blood cancer, expected to take 4,650 lives in the United States this year. Most cases of CLL start in white blood cells called B-cells that have a protein called CD20 on their surface. In certain cases of CLL, a part of chromosome 17 is lost -- a deletion -- and along with it an important gene that controls apoptosis called p53. The 17p deletion is found in 3 to 10 percent of previously untreated cases and approximately 30 to 50 percent of relapsed or refractory cases – i.e., tumors bearing the 17p deletion tend to be harder to treat.

Strategies to improve treatment of CLL include "optimizing the weapon" used on a known target -- and this is being explored in the case of Gazyva. Another strategy is to help cancer cells "rediscover" an appropriate response to death signals, and this angle is being explored using venetoclax.

Results with Gazyva – the CLL11 Study

The CLL11 investigates the efficacy and safety profile of Gazyva plus chlorambucil, Rituxan plus chlorambucil and chlorambucil alone in 781 people with previously untreated CLL.

Updated results from the pivotal CLL11 study presented at this year’s ASH showed that after receiving the set 6-month regimen of Gazyva + chlorambucil, people remained treatment-free for nearly 4 years on average before needing their next treatment.

“These updated CLL11 data confirmed that Gazyva helped people with previously untreated chronic lymphocytic leukemia live significantly longer without disease worsening or death compared to Rituxan,” said Sandra Horning, M.D., Genentech’s chief medical officer and head of Global Product Development.

“After a fixed course of therapy with Gazyva, people remained treatment-free for nearly four years on average. Time free from treatment is an important consideration for a disease like CLL, which occurs in older adults who frequently have other health issues.”

Gazyva Safety Study

An ongoing study called GREEN is evaluating the safety and efficacy of Gazyva alone or in combination with chemotherapy, including bendamustine, in people with previously untreated or relapsed/refractory CLL.

There were no unexpected safety signals when Gazyva was combined with bendamustine. In addition, nearly 80 percent of people responded to treatment with Gazyva plus bendamustine, and a third of people achieved a complete response. A substantial number of people were also minimal residual disease (MRD)-negative when measured in the bone marrow or blood (28 percent and 59 percent, respectively), which means no cancer can be detected using a specific test.

Results with Venetoclax - M13-982 Study

Blocking a protein called BCL-2 may restore the signaling system that tells cancer cells to self-destruct. The BCL-2 protein is made, or expressed, by CLL cells as well as certain non-Hodgkin’s lymphoma cells.

Results with venetoclax, an investigational BCL-2 inhibitor, showed a nearly 80 percent overall response rate in patients with relapsed or refractory CLL with 17p deletion, a hard-to-treat form of a common adult leukemia.

Based in part on these results, Genentech’s partner AbbVie has submitted a New Drug Application to the FDA under breakthrough therapy designation. Timed with ASH 2015, a big annual cancer research meeting, the New England Journal of Medicine published positive results for a separate study of venetoclax in previously treated CLL.

“The high response rates, including complete responses and duration of response, demonstrate the potential of venetoclax to help people with this hard-to-treat type of leukemia,” said Genentech’s Sandra Horning, M.D., chief medical officer and head of Global Product Development. “This is a patient population that has very few treatment options, and we are working with AbbVie to bring this new option to people as quickly as possible.”

The results show:

  • Overall response rate nearly 80 percent (79.4 percent with venetoclax)
  • 7.5 percent of people achieved a complete response with or without complete recovery (complete response without normal blood counts) in the bone marrow (CR/CRi).
  • 45 people were tested to detect minimal residual disease in the blood.
  • 18 people achieved tested negative, meaning no cancer could be detected using a specific test.
  • 10 of these 18 people also had bone marrow tests and 6 were negative.

At one year:

  • 84.7 percent of all responses were maintained -- 94.4 percent of the responses were maintained in the group of people who had tested as having no minimal residual disease.
  • The one-year progression-free survival and overall survival rates were 72 percent and 86.7 percent, respectively.

No unexpected safety signals were reported.:

  • The most common Grade 3-4 adverse events were low white blood cell count (40 percent), low red blood cell count (18 percent), and low platelet count (15 percent).
  • Grade 3 or higher infection occurred in 20 percent of people. Laboratory tumor lysis syndrome was reported in five people; none had clinical consequences.

Data for venetoclax as a single drug or in combinations with other medicines across multiple blood cancers, including CLL, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM) and acute myeloid leukemia (AML) are also forthcoming.


Abstract #1733 Updated Survival Analysis from the CLL11 Study: Obinutuzumab Versus Rituximab in Chemoimmunotherapy-Treated Patients with Chronic Lymphocytic Leukemia. Accessed December 2015.

Abstract #493 Safety and Efficacy of Obinutuzumab Plus Bendamustine in Previously Untreated Patients with Chronic Lymphocytic Leukemia: Subgroup Analysis of the Green Study.

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