Longest Follow-Up Data Reported for Kite’s Tecartus® CAR T-Cell Therapy at ASH 2024 Reinforce Durable Efficacy and Survival Benefits
– Only CAR T to Demonstrate Prolonged Overall Survival After Five Years Follow-Up in Relapsed/Refractory Mantle Cell Lymphoma –
– ZUMA-2 Analysis Shows
– Real-World Evidence Analysis Shows High Effectiveness and Safety Profile Consistent with ZUMA-3 in Broader Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia Population –
The data presented include an oral presentation (Abstract # 748) of a primary analysis of ZUMA-2 cohort 3 demonstrating an overall response rate (ORR) of
“We are proud to share long-term data that continue to underscore durable efficacy and survival benefits with one-time treatment of Tecartus in people with relapsed or refractory mantle cell lymphoma and B-cell precursor acute lymphoblastic leukemia,” said Dominique Tonelli, VP, Global Head of Medical Affairs, Kite. “This compelling efficacy is consistent across patient subgroups and is observed in the latest follow-up analyses. Additionally, Kite’s industry-leading manufacturing shows that Tecartus can be successfully manufactured and elicit robust objective response rates regardless of white blood cell or lymphocyte count.”
Detailed Information on Tecartus Abstracts:
Abstract #748
Primary Analysis of ZUMA-2 Cohort 3: Brexucabtagene Autoleucel (Brexu-Cel) in Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Who Were Naive to Bruton Tyrosine Kinase Inhibitors (BTKi)
ZUMA-2 is a single-arm, multicenter, open-label Phase 2 study that investigated leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BKTi ibrutinib or acalabrutinib. Cohort 3 of ZUMA-2 assesses treatment of Tecartus in 86 patients who have not received treatment with a BTKi.
With a median follow-up of 15.5 months (range, 1.4-27.1), the primary endpoint was met with an ORR of
This efficacy was durable: Preliminary follow-up shows median duration of all time-to-event endpoints has not been met. The 12-month (
“For years, we have seen strong, durable responses with brexu-cel from patients previously exposed to BTKi treatment,” said Dr. Tom van Meerten, lead investigator, University Medical Center Groningen, Netherlands. “Patients with high-risk relapsed/refractory mantle cell lymphoma have poor outcomes, so it is encouraging to see positive results even in people who are BTKi-naïve. The high overall response rate, complete responses, and durable benefit demonstrated in ZUMA-2 cohort 3 indicate that brexu-cel can be used earlier in the treatment of relapsed/refractory mantle cell lymphoma.”
No new safety signals were detected, with a low rate of Grade ≥ 3 cytokine release syndrome (CRS) occurring in five patients (
Abstract #4388
Five-Year Outcomes of Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated With Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 Cohorts 1 and 2
The abstract features five-year follow-up data from cohort 1 of the ZUMA-2 study. Cohort 1 enrolled 68 patients who received the pivotal dose (2×106 anti-CD19 CAR T cells/kg) of Tecartus and received at least two prior lines of therapy. In addition, cohort 2 was designed in 2018 to assess a lower dose (0.5 x 106 anti-CD19 CAR T cells/kg) in the same line setting; however, the risk/benefit ratio of the cohort 1 dose was deemed optimal before cohort 2 reached full enrollment. In the primary analysis of cohort 2, 14 patients treated with Tecartus with a median follow-up of 16.0 (13.9-18.0) months demonstrated an ORR of
In the five-year analysis, median follow-up for cohorts 1 and 2 were 67.8 months (58.2-88.6) and 72.3 months (70.1-74.3), respectively. Median (
No new safety signals were detected, and no secondary T‑cell malignancies were reported at any time in ZUMA-2
“More than three years after its approval, brexu-cel continues to deliver in relapsed/refractory mantle cell lymphoma,” said Dr. Michael Wang, lead investigator, The University of Texas MD Anderson Cancer Center. “It is encouraging to see these results in a heavily pre-treated population and consistency across both cohorts.”
Abstract # 5092
Real-World Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) by High-Risk Features and Prior Treatments: Updated Evidence From the CIBMTR Registry
This real-world analysis of 242 evaluable adult R/R B-ALL patients treated with Tecartus from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry demonstrated the high effectiveness of CAR T-cell therapy in a broad R/R B-ALL patient population.
With a median follow-up of 7.2 months, the CR/CRi (CR with incomplete hematologic recovery) after Tecartus treatment was
Among all patients (n=242), rates of any grade CRS and ICANS by 100 days were
“In this real-world analysis of brexu-cel, we see an efficacy and safety profile consistent with the findings of the pivotal ZUMA-3 study in relapsed/refractory B-cell acute lymphoblastic leukemia, but in a broader patient population,” said Dr. Kitsada Wudhikarn, lead investigator, Associate Professor of Medicine, Division of Hematology, Chulalongkorn University,
Abstract #4193
Impact of Disease Burden, CAR-T Expansion, and Mononuclear Cell Recovery on Overall Response and Duration of Response in ZUMA-3 Pivotal Study
In the analysis, researchers evaluated clinical and pharmacokinetic/pharmacodynamic data in the context of best response and durability of response among 78 R/R B-ALL patients who received Tecartus in the ZUMA-3 study.
Tecartus was successfully manufactured from apheresis material and elicited robust rates of objective response regardless of white blood cell or lymphocyte count. Half of the patients who achieved duration of response lasting >12 months had a bone marrow blast percentage of ≥
Additionally, CAR expansion within the first month post Tecartus infusion is associated with best response as well as durable response, even without persistence of CAR T cells. Recovery of mononuclear cells post infusion also appeared higher in subjects with longer response. These findings have the potential to support treatment decision-making, such as the need for subsequent allogeneic stem cell transplant as consolidation of remission.
About ZUMA-2
The ongoing, single-arm, open-label ZUMA-2 pivotal study enrolled 86 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint was objective response rate per the Lugano Classification (2014), defined as the combined rate of CR and partial responses as assessed by an Independent Radiologic Review Committee (IRRC).
Secondary endpoints include DOR, best objective response, PFS, OS, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score.
About ZUMA-3
ZUMA-3 is an ongoing international multicenter (
About MCL
MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the “mantle zone” of the lymph node and predominantly affects men over the age of 60. Approximately 33,000 people worldwide are diagnosed with MCL each year. MCL is highly aggressive following relapse, with many patients’ disease progressing following therapy.
About ALL
ALL is an aggressive and rare type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. While
About Tecartus
Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide.
Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
- Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
-
Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
- Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
- Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed.
- T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies
- Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. CRS occurred in
Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. 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 Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in
The most common neurologic events (>
Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.
REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that:
- Healthcare facilities that dispense and administer Tecartus 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 two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus.
Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. Infections (all grades) occurred in
Febrile neutropenia was observed in
In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed.
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 Tecartus infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in
Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in
The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment with Tecartus.
Secondary Malignancies may develop. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that one 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 Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period.
Adverse Reactions: The most common non-laboratory adverse reactions (≥
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in
Forward-Looking Statements
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 the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Tecartus (such as ZUMA-2, ZUMA-3 and real-world analysis); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; Gilead and Kite’s ability to timely and successfully manufacture and deliver Tecartus, or produce an amount of supply sufficient to satisfy demand for Tecartus; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as filed with the
Tecartus, Gilead, the Gilead logo, Kite, the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies.
For more information on Kite, please visit the company’s website at www.kitepharma.com. Follow Kite on social media on X (@KitePharma) and LinkedIn.
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Blair Baumwell, Gilead Media
public_affairs@gilead.com
Jacquie Ross, Investors
investor_relations@gilead.com
Source: Gilead Sciences, Inc.