SANTA MONICA, Calif. / Dec 09, 2024 / Business Wire / Kite, a Gilead Company (Nasdaq: GILD), announced results today from four analyses that continue to demonstrate the durability of response of Tecartus® (brexucabtagene autoleucel) in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) and relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.
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 91% and complete response (CR) rate of 73% in Bruton tyrosine kinase inhibitor (BTKi)-naïve patients with R/R MCL. Long-term follow-up of patients in ZUMA-2 cohorts 1 and 2 (Abstract #4388), showed that 39% of patients with R/R MCL were still alive after five years, underscoring Tecartus as the only CAR T to have five-year follow-up data in this patient population. In addition, real-world evidence outcomes in adults with R/R B-ALL treated with Tecartus (Abstract # 5092 and #4193) demonstrated a high effectiveness and consistent safety profile in a broader patient population than the pivotal ZUMA-3 study.
“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 91% (95% CI, 82.5-95.9; P<.0001). Seventy three percent (95% CI, 62.6-82.2) of patients had a CR, 17% (95% CI, 10.1-27.1) had a partial response (PR), 3% (95% CI, 0.7-9.9) had stable disease, and 3% (95% CI, 0.7-9.9) had progressive disease (PD) as best response to Tecartus.
This efficacy was durable: Preliminary follow-up shows median duration of all time-to-event endpoints has not been met. The 12-month (95% CI) duration of response (DOR), progression-free survival (PFS), and overall survival (OS) rates were 80% (69.1-87.9), 75% (64.5-83.4), and 90% (80.7-94.4), respectively.
“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 (6%) and an expected rate of Grade ≥ 3 neurological events (immune effector cell-associated neurotoxicity syndrome [ICANS]), occurring in 18 patients (21%).
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 93% (95% CI, 66.1-99.8) per independent radiology review committee (IRRC); 64% had a CR (95% CI, 35.1-87.2), and 29% had a PR (95% CI, 8.4-58.1).
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 (95% CI) investigator-assessed DOR and PFS were 36.5 months (17.7-48.9; n=60; 17 patients in ongoing response, all CR) and 25.3 months (12.7-46.6; n=68) in cohort 1; and 57.5 months (4.7-not estimable [NE]; n=12; 3 patients in ongoing response, all CR) and 29.5 months (3.3-NE; n=14) in cohort 2. Median OS (95% CI) and 60-month OS rates (95% CI) were 46.5 months (24.9- 60.2) and 39% (26.7-50.1) in cohort 1, respectively; and not reached (9.4-NE) and 54% (23.8-76.2) in cohort 2, respectively.
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 80% (95% CI, 75-85; 68% [60-76] for 145 patients not in CR/CRi pre-infusion). Estimated six-month rates (95% CI) of DOR were 67% (58-74; n=192; 66% [51-77] in 99 patients not in CR/CRi pre-infusion), six-month rates of relapse-free survival (RFS) were 55% (95% CI, 48-62; n=242), and six-month rates of OS were 80% (95% CI, 74-84; n=242).
Among all patients (n=242), rates of any grade CRS and ICANS by 100 days were 81% (95% CI, 76-86; 13% Grade ≥3 [95% CI, 9-18]), and 46% (95% CI, 39-52; 24% Grade ≥3 [95% CI, 19-30]), respectively. Day 30 prolonged thrombocytopenia and neutropenia rates were 30% (95% CI, 24-36) and 34% (95% CI, 28-41), respectively.
“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, Bangkok, Thailand. “Notably, the high level of effectiveness seen in the patient registry was consistent across prior treatments and most high-risk features. These findings provide further evidence of the substantial utility of brexu-cel in the treatment of this challenging blood cancer.”
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 ≥50%, demonstrating the potential of Tecartus to benefit patients regardless of disease burden.
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 (U.S., Canada, Europe), single-arm, open-label, registrational Phase 1/2 study of Tecartus in adult patients (≥18 years old) with B-ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation. The primary endpoint is the rate of overall complete remission or complete remission with incomplete hematological recovery by central assessment. Duration of remission and RFS, OS, minimal residual disease negativity rate, and allogeneic stem cell transplantation rate were assessed as secondary endpoints.
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 80% of ALL occurs in children, it represents a devastating disease in adults. In adults, B-cell precursor ALL is the most common form, accounting for 75% of cases. Survival rates in adults with R/R B-ALL are poor, with median OS at less than eight months.
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:
U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was five days (range: 1 to 12 days) and the median duration of CRS was eight days (range: 2 to 63 days) for patients with ALL.
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 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus.
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:
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 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of “febrile neutropenia” (11 (14%)) plus the concurrent events of “fever” and “neutropenia” (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.
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 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion.
Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.
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 (≥ 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions (≥ 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis.
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on achieving cures with cell therapy. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial supply and commercial product manufacturing. For more information on Kite, please visit www.kitepharma.com.
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 Foster City, Calif. Gilead acquired Kite in 2017.
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 U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.
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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December 17, 2024 December 13, 2024 | |
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