Pivotal Phase III CLL14 Results for Venclexta in Combination with Gazyva for Chronic Lymphocytic Leukemia Presented at ASCO 2019 and Published in the New England Journal of MedicineSource: Business Wire
– Venclexta plus Gazyva showed improvements across multiple efficacy measures compared to Gazyva plus chlorambucil, including progression-free survival and deep remissions as determined by minimal residual disease measurement –
– This 12-month, fixed-duration, chemotherapy-free combination was recently approved for previously untreated chronic lymphocytic leukemia under the FDA’s Real-Time Oncology Review pilot program –
At two years, one year after stopping treatment, nearly nine out of ten patients (88.2 percent) in the Venclexta plus Gazyva arm remained progression-free, compared to 64.1 percent in the Gazyva plus chlorambucil arm. Safety for Venclexta plus Gazyva appeared consistent with the known safety profiles of the individual medicines. Common Grade 3-4 adverse events with Venclexta plus Gazyva compared to Gazyva plus chlorambucil, respectively, were low white blood cell count (52.8 percent vs. 48.1 percent) and infections (17.5 percent vs. 15.0 percent).
“The results of our Phase III CLL14 trial, reported today at
The treatment benefit demonstrated with the Venclexta plus Gazyva combination compared to Gazyva plus chlorambucil was consistent across secondary endpoints, including:
- Overall response (84.7 percent vs. 71.3 percent; p<0.001)
- Complete response with at least partial blood count recovery (49.5 percent vs. 23.1 percent; p<0.001)
- Minimal residual disease (MRD)-negativity in the bone marrow (56.9 percent vs. 17.1 percent; p<0.001) and peripheral blood (75.5 percent vs. 35.2 percent; p<0.001) three months after treatment. MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than one CLL cell in 10,000 white blood cells.
These data were presented at the 2019 ASCO Annual Meeting on
Venclexta is being developed by
About the CLL14 Study
CLL14 (NCT02242942) is a randomized Phase III study evaluating the
combination of fixed-duration Venclexta plus Gazyva compared to Gazyva
plus chlorambucil in patients with previously untreated chronic
lymphocytic leukemia (CLL) and co-existing medical conditions.
Co-existing medical conditions included reduced kidney function or
co-morbidities assessed by a standard scale (Cumulative Illness Rating
Scale). 432 patients with previously untreated CLL 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
alongside 12-month duration of chlorambucil (Arm B). Arm A started with
an initial dosing of Gazyva followed by a five-week Venclexta dose
ramp-up to help reduce the risk of tumor lysis syndrome. The primary
endpoint of the study is investigator-assessed progression-free survival
(PFS). Secondary endpoints include PFS assessed by independent review
committee (IRC), minimal residual disease (MRD) status, overall response
rate (ORR), complete response (with or without complete blood count
recovery), overall survival, duration of response, event-free survival,
time to next CLL treatment, and safety. The CLL14 study is being
conducted in cooperation with the
After a median follow-up of 28 months, results showed:
Patients who received Venclexta plus Gazyva lived significantly longer
without their disease worsening (PFS, as assessed by investigator)
compared to those who received Gazyva plus chlorambucil (HR 0.35; 95
percent CI 0.23-0.53; p<0.001).
- At two years, 88.2 percent of patients in the Venclexta plus Gazyva arm had not experienced disease progression, compared to 64.1 percent with Gazyva plus chlorambucil.
- Median PFS reported by investigators was not yet reached in either arm. IRC assessment of PFS was consistent (HR 0.33; 95 percent CI, 0.22-0.51; p<0.001).
- Clinical benefit observed for Venclexta plus Gazyva compared to Gazyva plus chlorambucil was consistent across secondary endpoints, including ORR (84.7 percent vs. 71.3 percent; p<0.001) and CR including incomplete marrow recovery (49.5 percent vs. 23.1 percent; p<0.001).
- In addition, higher rates of MRD-negativity in the bone marrow (56.9 percent vs. 17.1 percent; p<0.001) and peripheral blood (75.5 percent vs. 35.2 percent; p<0.001) were observed three months after treatment with Venclexta plus Gazyva compared to Gazyva plus chlorambucil. MRD-negativity was defined as less than one CLL cell in 10,000 leukocytes.
- Safety for Venclexta plus Gazyva appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Common Grade 3-4 adverse events with Venclexta plus Gazyva compared to Gazyva plus chlorambucil, respectively, were low white blood cell count (52.8 percent vs. 48.1 percent) and infections (17.5 percent vs. 15.0 percent).
Chronic lymphocytic leukemia (CLL) is the most common type of adult
In CLL, the cancer primarily occurs in the blood and bone marrow. Small lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in the lymph nodes.
Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. 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.
Venclexta is being developed by
Gazyva 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. Gazyva was discovered by Roche Innovation Center
Additional combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.
Venclexta is a prescription medicine used:
- To treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
In combination with azacitidine, or decitabine, or low-dose cytarabine
to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ Are 75 years of age or older, or
‒ Have other medical conditions that prevent the use of standard chemotherapy.
It is not known if Venclexta is safe and effective in children.
Important Safety Information
Venclexta can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids through their vein.
The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.
Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.
Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose, on the day of the first dose of Venclexta, and each time a dose is increased.
The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects.
Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased tumor lysis syndrome.
- Patients must tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other, causing serious side effects.
- Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:
- Have kidney problems.
- Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
- Have a history of high uric acid levels in the blood or gout.
- Are scheduled to receive a vaccine. The patient should not receive a “live vaccine” before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
- Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
- Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients should not breastfeed during treatment with Venclexta.
What to avoid while taking Venclexta:
Patients should not drink grapefruit juice, eat grapefruit,
Venclexta can cause serious side effects, including:
- Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta.
- Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.
The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell counts; low platelet counts; low red blood cell counts; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of your arms, legs, hands, and feet.
The most common side effects of Venclexta in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.
Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.
These are not all the possible side effects of Venclexta. Patients should tell their doctor about any side effect that bothers them or that does not go away.
Gazyva® (obinutuzumab) is a prescription medicine used:
- With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
- With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
- With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information
The most important safety information patients should know about Gazyva
Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:
- Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
- Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.
Who should not receive Gazyva:
Patientsshould NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva.Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.
Additional possible serious side effects of Gazyva:
Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:
- Infusion Reactions: Theseside effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
- Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
- Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
- Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
- Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
- Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.
The safety of Gazyva was evaluated based on 392 patients with relapsed
A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent).The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.
Before receiving Gazyva, patients should talk to their doctor about:
- Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
- Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
Patients should tell their doctor about any side effects.
These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.
Gazyva is available by prescription only.
Founded in 1996 and headed by
About Genentech in Hematology
For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.
Founded more than 40 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious and life-threatening medical
conditions. The company, a member of the
Priscilla White, (650) 467-6800
Eydith Comenencia Ortiz, (650) 745-5210
Loren Kalm, (650) 225-3217
Karl Mahler, +41 61 687 85 03