NEW ANALYSES PRESENTED AT ASH 2023 SUPPORT THE POTENTIAL LONG-TERM RESPONSE AND SAFETY OF KITE’S TECARTUS® (BREXUCABTAGENE AUTOLEUCEL) IN PATIENTS WITH AGGRESSIVE BLOOD CANCERS

NEW  ANALYSES  PRESENTED  AT  ASH  2023  SUPPORT  THE POTENTIAL  LONG-TERM  RESPONSE  AND  SAFETY  OF  KITE’S  TECARTUS^®  (BREXUCABTAGENE AUTOLEUCEL)  IN  PATIENTS  WITH  AGGRESSIVE  BLOOD  CANCERS

 

– At Almost Four Years of Follow-up in the Pivotal ZUMA-2 Study, Median Overall Survival was 46.4 Months, Supporting Long-term Response in Adult Patients with Relapsed/Refractory(R/R) Mantle Cell Lymphoma (MCL) –

 

– Real-world Evidence (RWE) Shows Effectiveness in Adult R/R MCL with a Complete Response Rate of 81% and 84% for High-risk Features (Patients with TP53 /17p Deletion) –

 

– RWE also Shows Complete Remission/ Complete Remission with Incomplete Haematological Recovery (CRi) Rate of 76% in Adult Patients with R/R B-cell Precursor Acute Lymphoblastic Leukaemia (B-ALL)–

 

 

Stockley Park, UK – 11 December 2023 – Kite, a Gilead Company, today announced the results of four new analyses supporting the use of Tecartus^® (brexucabtagene autoleucel) in relapsed/refractory mantle cell lymphoma (R/R MCL) and relapsed/refractory adult B-cell precursor acute lymphoblastic leukaemia (R/R B-ALL). These results include four-year overall survival (OS) data from the pivotal ZUMA-2 study and primary results from ZUMA-18, an expanded access study, evaluating the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel in patients with R/R MCL, presented orally (Abstract #106) at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition.

 

An analysis from ZUMA-2 showing that patients who received early versus late intervention for management of cytokine release syndrome (CRS) and neurological events experienced improved safety outcomes was also presented in a poster session (Abstract #2120).

 

In addition, real-world findings on effectiveness and safety outcomes from the Center for International Blood & Marrow Transplant Research (CIBMTR) observational database of U.S. patients who received brexucabtagene autoleucel for R/R MCL (Abstract #107) were highlighted in an oral session; CIBMTR data from adult patients with R/R B-ALL (Abstract #1029) were also presented orally today. 

 

“The clinical results and real-world evidence presented at ASH clearly support the potential for long-term response and safety of brexucabtagene autoleucel in aggressive blood cancers for which patients have limited treatment options,” said Frank Neumann, MD, PhD, Senior Vice President, Global Head of Clinical Development, Kite. “We are particularly encouraged that the real-world evidence demonstrates consistent outcomes for brexucabtagene autoleucel among a broader range of patients.”

 

(Abstract # 106)

Outcomes of Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated with Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 and ZUMA-18, an Expanded Access Study

 

At a median follow-up of 47.5 months in all 68 patients with R/R MCL who had previously received anthracycline or bendamustine-containing chemotherapy, an anti CD20 antibody, and a Bruton’s tyrosine kinase inhibitor (BTKi, ibrutinib or acalabrutinib), and were treated with brexucabtagene autoleucel in the pivotal ZUMA-2 study, median OS was 46.4 months with 30 patients (44%) still alive at data cutoff. Median OS for patients with complete response (CR, n=46) was 58.7 months.[i]

 

Efficacy and safety outcomes for 23 patients with R/R MCL enrolled in ZUMA-18, a multicentre, open-label, expanded access study of brexucabtagene autoleucel, were also presented. With a median follow-up of 33.5 months, the investigator-assessed objective response rate (ORR) was 87% (95% Confidence Interval [CI], 66.4-97.2); 57% had a CR (95% CI, 34.5-76.8), 30% had a partial response (95% CI, 13.2-52.9), and 9% had progressive disease as their best response to brexucabtagene autoleucel. The median OS was not reached (95% CI, 10.4-not estimable) at data cutoff with a 58% OS rate at 24 months.ⁱ 

 

At the data cutoff, 61% of patients were still alive. All 23 patients who received brexucabtagene autoleucel in ZUMA-18 experienced at least one Grade ≥3 adverse event (AE); Grade ≥3 cytokine release syndrome (CRS) and neurological events occurred in one patient (4%) and eight patients (35%), respectively. Five Grade 5 AEs occurred, one that was deemed related to brexucabtagene autoleucel therapy (multiple organ dysfunction syndrome on Day 20) and four that were deemed unrelated to brexucabtagene autoleucel therapy (sepsis [2, Days 123 and 219], aspiration [1, on Day 49], and encephalopathy [1, on Day 68]).ⁱ

 

“Consistent with ZUMA-2 findings, which showed a median overall survival of 46.4 months in patients with a complete response, brexu-cel demonstrated similar efficacy in relapsed/refractory mantle cell lymphoma patients in the ZUMA-18 expanded access study, with fewer cases of cytokine release syndrome,” said Andre Goy, MD, ZUMA-2 investigator and Lymphoma Division Chief, John Theurer Cancer Center, Hackensack University Medical Center.  “Together, the results of these two studies provide strong support for the continued use of brexu-cel in the relapsed/refractory mantle cell lymphoma setting.”

 

(Abstract # 107)

Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR Subgroup Analysis of High-Risk Characteristics

 

Adult patients with R/R MCL and TP53 mutation/deletion or high Ki-67 proliferation index (PI) have historically had limited treatment options with dismal outcomes. In a previously presented three-year follow-up of ZUMA-2, outcomes were comparable across various high-risk subgroups, including in patients with TP53 mutation or Ki-67 PI ≥ 30% or ≥ 50%.[ii]

 

An analysis of a CIBMTR observational database of R/R MCL patients receiving brexucabtagene autoleucel from 84 U.S. centres was presented. With a median follow-up of 12.2 months, CR rates were high among these challenging-to-treat
sub-populations:ⁱⁱ

·     For patients with deletion of TP53/17p (n=44), CR was 84% compared to 81% in those without (n=183)

·     For patients with Ki-67 PI ≥ 50% (n=146), CR was 83% vs 84% in those with Ki-67 PI < 50% (n=111).

 

Safety endpoints were largely consistent among all subgroups. Prolonged neutropenia and thrombocytopenia occurred more frequently in patients with vs without deletion of TP53/17p (25% vs 13% and 28% vs 17%, respectively). Grade ≥ 3 CRS occurred more frequently in ZUMA-2-ineligible vs eligible pts (13% vs 7%). After multivariable adjustment, all effectiveness and most safety outcomes were consistent regardless of deletion of TP53/17p and Ki-67 >+50%.ⁱⁱ

 

“These real-world findings suggest that outcomes of brexu-cel treatment, including a high complete response rate, are largely consistent, regardless of ZUMA-2 eligibility or the high-risk feature subgroups analysed. Although patients without deletion of TP53/17p appeared to have longer overall survival than patients with, the data further demonstrate the safety and durability of response of brexu-cel for patients with relapsed/refractory mantle cell lymphoma, who typically face poor prognoses and have limited treatment options,” said Swetha Kambhampati, MD, lead investigator, City of Hope assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation.

 

(Abstract # 1029)

Real-world Outcomes of Brexucabtagene Autoleucel (brexu-cel) for Relapsed or Refractory (R/R) Adult

B-cell Acute Lymphoblastic Leukemia (B-cell ALL): Evidence from the CIBMTR registry

 

This real-world evidence study of brexucabtagene autoleucel in adult patients with B-ALL examined a CIBMTR registry database of 150 patients across 67 centres in the United States.[iii]

 

The assessment found the overall complete remission or complete remission with incomplete haematological recovery (CR/CRi) rate by Day 100 post infusion was 76%, and 70% were still in remission at 6 months post initial response (95% CI: 55-80). For those who were not in response prior to lymphodepletion (LD), 63% of these patients converted to a CR/CRi post infusion.ⁱⁱⁱ

 

The OS rate at six months was 78% (95% CI: 69-84); primary causes of death were primary disease (n=13/32, 41%) and infection (n=7/32, 22%). About one third (31%) of responders received a subsequent allogeneic stem cell transplant (alloSCT). High response rates were observed in all patients regardless of age, prior exposure to blinatumomab, prior alloSCT, or the presence of extramedullary disease prior to LD. Grade ≥3 CRS and immune effector cell-associated neurotoxicity syndrome (ICANS, ASTCT consensus) occurred in 9% and 24% of patients, respectively.  Treatment for CRS and/or ICANS consisted mainly of tocilizumab (67%) and corticosteroids (51%). Most of these AEs were resolved within three weeks of infusion (CRS, 94%; ICANS, 80%). Prolonged cytopenia and neutropenia 30 days post infusion were experienced by 42% and 33% of patients, respectively.ⁱⁱⁱ

 

“It is encouraging to see that the efficacy and safety outcomes of the largest real-world evidence study of brexu-cel in B-ALL are consistent with the results of the ZUMA-3 study, with high response rates in a broad, actual patient population,” said Evandro Bezerra, MD, lead investigator, haematology specialist, Ohio State University Comprehensive Cancer Center. “These findings further build our confidence in the role of brexu-cel in treating adult patients with B-ALL, including those living with high-risk comorbidities and other factors that make treatment particularly challenging.”

 

About ZUMA-2

ZUMA-2 is a single-arm, international multicentre (US and Europe), open-label Phase 2 study involving 74 enrolled/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 BTK inhibitors ibrutinib or acalabrutinib. The objectives of the study are to evaluate the efficacy and safety (68 patients) after a single infusion of brexucabtagene autoleucel in this patient population. The primary endpoint for the study is objective response rate which is defined as the combined rate of complete responses and partial responses as assessed by an Independent Radiology Review Committee.

 

Secondary endpoints include duration of response, best objective response, progression-free survival, OS, incidence of AEs, 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. The study is ongoing.

 

About ZUMA-18

The U.S. expanded access ZUMA-18 trial consists of two cohorts of 27 patients per total. The primary objectives were to provide access to brexucabtagene autoleucel for patients with R/R MCL until it was commercially available (Cohort 1) and patients with R/R MCL whose manufactured product did not meet commercial release specifications (Cohort 2). In Cohort 1, adults (≥18 years) with R/R MCL with ≥1 prior regimen underwent leukapheresis and conditioning chemotherapy followed by a single infusion of brexucabtagene autoleucel at a target dose of 2×10⁶ cells/kg (or fixed dose of 2x10⁸ anti-CD19 CAR T cells for patients who are ≥100 kg). In Cohort 2, patients received Cohort 1 treatment without leukapheresis (initial leukapheresis product used). Key endpoints were safety, ORR, and OS.

 

About ZUMA-3

ZUMA-3 is an ongoing international multicentre (US, Canada, Europe), single arm, open label, registrational Phase 1/2 study of brexucabtagene autoleucel in adult patients (≥18 years old) with ALL whose disease is refractory to or has relapsed following standard systemic therapy or haematopoietic stem cell transplantation. The primary endpoint is the rate of overall complete remission (CR) or complete remission with incomplete haematological recovery (CRi) by central assessment. Duration of remission and relapse-free survival, overall survival, minimal residual disease (MRD) negativity rate, and alloSCT rate were assessed as secondary endpoints.

 

About Mantle Cell Lymphoma (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.[iv] ^,[v] Approximately 33,000 people worldwide are diagnosed with MCL each year including 7,400 in Europe.[vi] ^{,[vii] ,[viii] ,[ix]} MCL is highly aggressive following relapse, leading to disease progression in many patients following therapy.[x]

 

About Acute Lymphoblastic Leukemia (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.[xi] In adults, B-cell precursor ALL is the most common form, accounting for 75% of cases.[xii] Survival rates in adults with R/R B-ALL are poor, with a median OS of less than eight months.[xiii]

 

About Brexucabtagene Autoleucel

In December 2020, the European Commission (EC) granted conditional Marketing Authorisation for brexucabtagene autoleucel, the first CAR T-cell therapy approved in Europe for adult patients with relapsed or refractory mantle cell lymphoma after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor. In August 2022, the EC approved brexucabtagene autoleucel for the treatment of adult patients 26 years of age and above with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia.[xiv]

 

About CIBMTR

The Center for International Blood and Marrow Transplant Research (CIBMTR) is a non-profit research collaboration between the National Marrow Donor Program^® (NMDP)/Be The Match^® and the Medical College of Wisconsin (MCW). CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centres, and a unique database of long-term clinical data for more than 635,000 people who have received hematopoietic cell transplantation and other cellular therapies.[xv]

 

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. 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 production and commercial product manufacturing.

 

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 and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. 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 unfavourable results from ongoing or additional clinical studies, including those involving brexucabtagene autoleucel; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programmes and, as a result, these programmes may never be successfully commercialised for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, 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.

 

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Kite, the Kite logo, Tecartus, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.

 

 

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[i] Goy, A, et al. Outcomes of Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated with Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 and ZUMA-18, an Expanded Access Study. Presented at the 65^th ASH Annual Meeting and Exposition, 9-12 December 2023, San Diego, US 

^[ii] Kambhampati, S, et al. Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR Subgroup Analysis of High-Risk Characteristics. Presented at the 65^th ASH Annual Meeting and Exposition, 9-12 December 2023, San Diego, US 

^[iii] Bezerra, E, et al. Real-world Outcomes of Brexucabtagene Autoleucel (brexu-cel) for Relapsed or Refractory (R/R) Adult B-cell Acute Lymphoblastic Leukemia (B-cell ALL): Evidence from the CIBMTR registry. Presented at the 65th ASH Annual Meeting and Exposition, 9-12 December 2023, San Diego, US 

[iv] Dreyling M, Campo E, Hermine O, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2017 July; 28 (4): iv62-iv71. 

[v]  Sharma S & Sweetenham J. Mantle Cell Lymphoma: Are New Therapies Changing the Standard of Care? EMJ Oncol. 2018;6{1}:109-119.

[vi] NORD. Mantle Cell Lymphoma. https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Accessed: November 2023. 

[vii]  Leukemia & Lymphoma Society. NHL subtypes. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/diagnosis/nhl-subtypes. Accessed: November 2023. 

[viii] Globocan 2018. Europe fact sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf. Accessed: November 2023.

[ix]  Ferlay J, Colombet, M., Soerjomataram, I., et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. European Journal Of Cancer, 2018;103, 356-387. Available at: https://doi.org/10.1016/j.ejca.2018.07.005. Accessed: November 2023.

[x] Wang M, et al. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020;382:1331-1342.

[xi] Acute Lymphoblastic Leukemia in Adults - The EBMT Handbook - NCBI Bookshelf (nih.gov). Accessed: November 2023.

[xii] Acute lymphoblastic leukemia: a comprehensive review and 2017 update - PMC (nih.gov). Accessed: November 2023.

[xiii] Shah BD, Ghobadi A, Oluwole OO, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021;398(10299):491-502.

[xiv] European Medicines Agency. Tecartus^® (brexucabtagene autoleucel) SPC. Available at: https://www.ema.europa.eu/en/documents/product-information/tecartus-epar-product-information_en.pdf Accessed November 2023.

[xv] Center for International Blood & Marrow Transplant Research. Our Impact. Available at: https://cibmtr.org/CIBMTR/About/Our-Impact. Accessed: November 2023. 

 

 

 

 

 

 

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