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|Kite Announces New Data Analyses for CAR T Therapy in Patients with Blood Cancers at the 2018 American Society of Clinical Oncology Meeting|
-- ZUMA-1 Data Suggest Patient Response to Yescarta® (axicabtagene ciloleucel) at Three Months May be Predictive of Longer-Term Response in Refractory B-cell Lymphoma --
-- ZUMA-3 Analysis Suggests High Complete Response Rates with KTE-C19 in Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) Regardless of Prior Blinatumomab Treatment --
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“With the U.S. approval of Yescarta last year, we aim to transform the
treatment of patients with refractory large B-cell lymphoma,” said
Yescarta was the first CAR T cell therapy to be approved by the
Yescarta has a Boxed Warning in its product label and an associated Risk Evaluation and Mitigation Strategy (REMS) regarding the risks of CRS and neurologic toxicities. Please see below for Important Safety Information.
A Marketing Authorization Application (MAA) for axicabtagene ciloleucel
is currently under review with the
Ongoing Responses, Response by Prior Lines of Therapy in ZUMA-1 (Abstracts #3003 and #3039)
Long-term ZUMA-1 follow-up data have shown an overall response rate (ORR) of 83 percent (n=84/101), including 58 percent (n=59/101) of patients with a complete response at a median follow-up of 15.1 months. In this long-term follow-up, Grade 3 or higher cytokine release syndrome (CRS) and neurologic events were seen in 12 percent and 29 percent of patients, respectively.
A new analysis of ZUMA-1 suggests that response status three months
after infusion of Yescarta may be predictive of longer-term disease
control. Of the 42 patients with complete response and nine with partial
response at three months, the 12-month PFS rates were 79 percent and 78
percent, respectively. This abstract has also been selected for
inclusion in the 2018 Best of
“We are encouraged by the strong long-term complete response rates in
ZUMA-1, which represents a patient population that previously had few if
any remaining treatment options,” said
An additional ZUMA-1 analysis evaluated outcomes based on prior therapy the patients had received. The results indicate long-term clinical benefit for patients with refractory large B cell lymphoma, irrespective of the number of prior lines of therapy.
Rates of Response with Prior Blinatumomab Treatment in ZUMA-3 (Abstract #7006)
Phase 1 data for KTE-C19, an investigational CD19 CAR T cell therapy,
presented at the 2017 Annual Meeting of the
“As a CD19/CD3 bispecific T cell antibody, the possible impact of prior
blinatumomab use on the efficacy of KTE-C19 – a CD19-directed CAR T
therapy – was an important question for exploration,” said
Grade 3 or higher CRS was seen in 27 percent of patients with prior blinatumomab and in 17 percent of patients without prior blinatumomab. Grade 3 or higher neurologic events were seen in 36 percent of patients with prior blinatumomab and 67 percent of patients without prior blinatumomab. A greater number of subjects in the blinatumomab-naïve group received the higher 1 × 106 cells/kg dose.
KTE-C19 for ALL is investigational and has not been proven safe or efficacious.
U.S. Important Safety Information for Yescarta
BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of patients, including 13% with ≥ Grade 3. Among patients who died after receiving Yescarta®, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta®. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.
NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks, with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade 3 or higher occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta®. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta®. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.
YESCARTA® REMS: Because of the risk of CRS and neurologic toxicities, Yescarta® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta® REMS. The required components of the Yescarta® REMS are: Healthcare facilities that dispense and administer Yescarta® must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta® infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta® are trained about the management of CRS and neurologic toxicities. Further information is available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS: Allergic reactions may occur. Serious hypersensitivity reactions including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta®.
SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta® should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta® infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.
PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta® infusion. Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta® infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta® infusion.
HYPOGAMMAGLOBULINEMIA: B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta® treatment, and until immune recovery following treatment.
SECONDARY MALIGNANCIES: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.
ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.
Please see accompanying full Prescribing Information, including BOXED WARNING and Medication Guide.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including Kite’s
ability to complete the Phase 3 study of Yescarta for the treatment of
relapsed or refractory large B-cell lymphoma (ZUMA-7) and the Phase 1/2
studies of KTE-C19 for the treatment of acute lymphoblastic leukemia and
other hematologic cancers in the currently anticipated timelines, or at
all. In addition, there is the possibility of unfavorable results from
additional clinical trials involving Yescarta and KTE-C19. Further, Kite
may be unable to obtain regulatory approval for axicabtagene ciloleucel
For more information on Kite, please visit the company’s website at www.kitepharma.com. Learn more about Gilead at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.