From The Editor | April 3, 2019

NDA Hopes To Speed New Combination Therapy To Leukemia Patients

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Leukemia (002)

In March 2019, Genentech announced the submission of a New Drug Application (NDA) to the U.S. FDA for Venclexta in combination with Gazyva. The combination therapy is for people with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. The FDA is reviewing the application under the Real-Time Oncology Review pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

Breakthrough Therapy Designation was granted based on results of the randomized Phase III CLL14 study, which evaluated the fixed-duration combination of Venclexta plus Gazyva, compared to Gazyva plus chlorambucil. The study met its primary endpoint and showed a statistically significant reduction in the risk of disease worsening or death (progression-free survival as assessed by investigator) compared to standard-of-care. Safety for the Venclexta plus Gazyva combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

I spoke with Nancy Valente, M.D., SVP, global hematology development at Genentech, about the NDA and what it could mean for leukemia patients.

Ed Miseta: What are the main challenges for leukemia patients taking part in clinical trials?

Nancy Valente: There are many challenges that people with leukemia face in managing their disease, which can also impact their participation in clinical trials. For people with chronic lymphocytic leukemia (CLL), the most common form of adult leukemia, age and co-existing medical conditions are factors to consider. The average age at CLL diagnosis is 70 years and as many as 89 percent of these patients will have other medical conditions, making them less likely to respond well to conventional treatments. This is why clinical trials are so important, but unfortunately, many people do not know that trials are even an option for them or are confused about how they can help. This is why we partnered with the American Cancer Society to develop an educational program called ACT: About Clinical Trials. With this information, we hope people facing leukemia or any other cancer can have more informed discussions with their families and physicians about their treatment options.

Miseta: How is ACT helping to educate patients?

Valente: About Clinical Trials is a program that helps educate people about cancer clinical trials and encourages them to discuss this option with their doctors and loved ones. The program helps address many of the issues people need to take into account when considering a clinical trial and shares resources to help patients locate clinical trials in their area. Patients can go to the website,, or call a toll-free number (1-877-970-7848) to speak with someone through a clinical trial matching service. The program is confidential and helps find trials most appropriate to a patient’s medical and personal situation. 

Miseta: What are the main findings of the Phase III CLL14 study?

Valente: The Phase III CLL14 study evaluated the fixed-duration, chemotherapy-free combination of Venclexta plus Gazyva in people with previously untreated CLL and co-existing medical conditions. The study met its primary endpoint and showed that this combination helped people live significantly longer without disease worsening or death (progression-free survival) compared to Gazyva plus chlorambucil, a current standard of care. Based on these findings, the FDA granted this combination Breakthrough Therapy Designation and is reviewing our supplemental New Drug Application under their Real-Time Oncology Review (RTOR) pilot program, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

Miseta: What is the potential impact for patients?

Valente: More than 20,000 people will be diagnosed with untreated CLL in the United States this year, and many are ineligible for intensive chemotherapy-based options. Results from the CLL14 study indicate that our novel BCL-2 inhibitor Venclexta plus Gazyva could provide a chemotherapy-free, fixed-duration treatment option for people with previously untreated CLL.

Miseta: Was there anything Genentech learned from this study that could be used to improve future trials for leukemia patients?

Valente: Venclexta plus Gazyva is a 12-month fixed-duration regimen – this means that patients did not have to receive treatment continuously or indefinitely. We are encouraged that this chemotherapy-free, fixed-duration combination is being reviewed by the FDA. This type of treatment administration could be valuable to patients and may be important to consider in the design of future clinical trials for people with CLL.

Miseta: Why are additional treatment options needed in this disease area?

Valente: There have been advances in treatment options for people with CLL. However, many patients cannot tolerate the side effects of standard chemotherapy treatments. This could be due to their age, health, or other factors. For that reason, additional treatment options are still needed.

Miseta: What other research is planned/ongoing for these medicines?

Valente: We are continuing to investigate both Venclexta in combination with approved and investigational molecules in a robust clinical development program across a range of blood cancers. As a testament to its potential, Venclexta has now been granted five Breakthrough Therapy Designations by the FDA: three in CLL and two in acute myeloid leukemia. Combination studies evaluating Gazyva with approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are also underway.