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39362711000001109

New Medicines

TecartusRelapsed or refractory mantle cell lymphoma (MCL)

Information

Tecartus
New molecular entity
Gilead Sciences
Kite

Development and Regulatory status

Launched
Approved (Licensed)
Launched
Yes
Feb 21Available for use in the NHS in England. The NHS has ten providers around the country which will be able to offer this treatment option [17].
Dec 20Approved in EU [15]
Oct 20Recommended for EU approval by CHMP - the full indication is "for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor. Tecartus should be prescribed by physicians experienced in the treatment of mantle cell lymphoma and must be administered in a qualified treatment centre by a physician with experience in the treatment of haematological malignancies and trained for administration and management of patients treated with Tecartus" [14].
Jul 20Approved in US for treatment of adult patients diagnosed with mantle cell lymphoma who have not responded to or who have relapsed following other kinds of treatment [13].
Jul 20Previously in Nov 19, orphan designation EU/3/19/2220 was granted by the European Commission to Kite Pharma EU B.V., Netherlands, for autologous peripheral blood T cells CD4 and CD8 selected and CD3 and CD28 activated transduced with retroviral vector expressing anti CD19 CD28/CD3-zeta chimeric antigen receptor and cultured (also known as KTE-X19 CAR) for the treatment of mantle cell lymphoma [12].
Feb 20Has breakthrough therapy status in US [11].
Feb 20Granted priority review in US [9].
Jan 20Filed in EU with Priority Medicines (PRIME) designation [8].
Dec 19Filed in the US. The manufacturer expects to file in the EU early 2020. [6]

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy produced ex vivo using a retroviral vector. Similar to axicabtagene but with a slightly different manufacturing process involving enrichment of lymphocytes needed for certain B-cell cancers.
Mantle cell lymphoma is a high-grade non-Hodgkin lymphoma (NHL). NHLs are a heterogeneous group of lymphoproliferative malignancies with differing patterns of behaviour and responses to treatment. MCL accounts for about 3-10% of all cases of NHL. MCL is more common in the over-50s and is three times more common in men than in women [3].
Relapsed or refractory mantle cell lymphoma (MCL)
Intravenous infusion

Further information

Yes

Trial or other data

Feb 21NICE approves use of Tecartus for MCL [17].
Jan 21In its final appraisal document, NICE recommends treatment with autologous anti-CD19-transduced CD3+ cells for use within the Cancer Drugs Fund as an option for treating r/r MCL in adults who have previously had a BTKi. It is only recommended if the conditions in the managed access agreement are followed. [16]
Dec 20Data released by the company in December 2020 from the PII ZUMA-2 trial (N=60), after a median follow up of 17.5 months, 92% achieved a response (ORR) with 67% achieving CR. Median duration of response (PFS and OS) were not yet reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic AEs were seen in 18% and 37% of patients, respectively; one fatal. CRS event No Grade 5 CRS/neurologic events occurred; there were two Grade 5 infectious AEs. [17]
Dec 20Data released by the company in December 2020 from the PII ZUMA-2 trial (N=60), after a median follow up of 17.5 months, 92% achieved a response (ORR) with 67% achieving CR. Median duration of response (PFS and OS) were not yet reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic AEs were seen in 18% and 37% of patients, respectively; one fatal. CRS event No Grade 5 CRS/neurologic events occurred; there were two Grade 5 infectious AEs. [17]
Apr 20PII ZUMA-2 study (n=74) is published; the objective response rate was 67% (95% CI 53-78%) in the primary analysis, with 57% in remission at a median follow-up of 12.3 months (range 7.0-32.3 months). Common grade >=3 adverse events included cytopenias (94%) and infections (32%) [10].
Jan 20No UK trials sites [7]
Dec 17NCT02601313 primary data now due Jul 18 [5]
Aug 17Kite is to be acquired by Gilead Sciences, with completion of the deal expected late 2017. It is not clear at present whether the Kite name will be retained for cell-based therapies [4].
Feb 17 PII ZUMA-2 study (NCT02601313) is currently recruiting patients and is expected to complete collection of primary outcome data in Sep 17 [2].
Nov 15Kite initiates the pivotal PII ZUMA-2 study to evaluate the efficacy of axicabtagene ciloleucel in patients with relapsed or refractory mantle cell lymphoma (NCT02601313). The study is expected to enrol approximately 70 subjects in the US, and the enrolment is expected to expand to EU [1].

Evidence based evaluations

TecartusB-precursor acute lymphoblastic leukaemia (ALL) in adults

Information

Tecartus
Licence extension / variation
Gilead Sciences
Kite

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Launched
Yes
Oct 21FDA grants approval for Tecartus (brexucabtagene autoleucel) for the treatment of adult patients (18 years and older) with relapsed or refractory B-cell precursor ALL. Patients can access Tecartus through 109 authorized treatment centers across the US. Tecartus is also under currently under review in the EU and UK for the treatment of adult patients with relapsed or refractory B-cell precursor ALL [13].
Jun 21Recently filed sBLA accepted for priority review in the US, with a target action date under the Prescription Drug User Fee Act (PDUFA) of October 1, 2021. Also has breakthrough therapy status for this indication [11].
Apr 21Kite submit sBLA to US FDA for treatment of adult with relapsed or refractory B-cell precursor ALL [10].
Nov 15Orphan designation (EU/3/15/1571) granted by the European Commission to Kite Pharma UK, Ltd, United Kingdom, for autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor for the treatment of acute lymphoblastic leukaemia [6].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy produced ex vivo using a retroviral vector. Similar to axicabtagene but with a slightly different manufacturing process involving enrichment of lymphocytes needed for certain B-cell cancers.
Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years. ALL represents 12% of all leukaemia (but 80% in children) [1].
B-precursor acute lymphoblastic leukaemia (ALL) in adults
Intravenous infusion

Further information

Yes

Trial or other data

Aug 21PII results of ZUMA-3 study (n=71) found a single infusion of KTE-X19 following leukapheresis and conditioning chemotherapy was associated with a 71% (95% CI 57–82) rate of complete remission (CR) or CR with incomplete haematological recovery [12].
Jun 21Results from the primary analysis of ZUMA-3 published in The Lancet and presented during an oral session at the 2021 ASCO Annual Meeting. Among treated patients (n=55), 47% had received three or more prior therapies. At a median follow-up of 16.4 months, 71% of treated patients achieved a complete response (CR) or CR with incomplete hematological recovery (CRi), with 31% in ongoing response at data cut-off. 97% of those responders had deep molecular remission, with undetectable minimal residual disease (MRD), and median overall survival (OS) among all responders was not reached. Among 25 patients with prior blinatumomab treatment, the CR/CRi rate was 60%. Among all treated patients, median duration of response (DOR), relapse-free survival (RFS), and OS were 12.8 months, 11.6 months and 18.2 months, respectively. Grade ≥3 adverse events occurred in 95% of patients, with anemia (49%) and pyrexia (36%) most frequently reported. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 24% and 25% of patients, respectively, and were generally reversed with treatment. Two Grade 5 treatment-related events occurred (one brain herniation and one case of septic shock) [11].
Nov 20PI/II ZUMA-3 trial completed collection of primary outcome data in Sep 20 as planned. Data have previously been presented from the PI part of the trial. A single intravenous infusion of KTE X19 demonstrated complete tumour remission in 25 of the 36 evaluable patients, with a median follow-up of 15.1 months (range 3.7 – 28.6 months). Out of 41 patients with ≥ 2 month of follow-up, 68% had CR/CRi complete response (CR) or CR with incomplete hematological recovery (CRi) and 73% of the patients had undetectable minimal residual disease (MRD). Also, out of 19 patients with ≥ 2-month of follow-up treated with 1 × 106 cells/kg, 16 (84%) had a CR/CRi and 12 patients (75 percent) were in ongoing response. The median event-free survival was 15 months. None of the responders, including those with high tumour burden and high risk genetic abnormalities, had a detectable minimal residual disease [8,9].
Sep 20In addition to the US, PI/II ZUMA-3 has already recruited patients in Canada, France, Germany and the Netherlands [7].
Sep 20PI/II ZUMA-3 study is no longer recruiting and expects to complete collection of primary outcome data this month [7].
Jan 20No UK trial sites [5]
Feb 19PI/II ZUMA-3 study (NCT02614066) now expected to complete collection of primary outcome data in Jan 20 [4].
Jan 18PI/II ZUMA-3 study (NCT02614066) is still recruiting & expects to complete collection of primary outcome data (overall complete remission rate) in Mar 19 [3].
Dec 15Kite Pharma initiates the pivotal PI/II ZUMA-3 study to evaluate axicabtagene ciloleucel in patients with relapsed or refractory B-precursor ALL (NCT02614066). Phase I part of the study will assess the safety of the product, whereas both efficacy and safety will be evaluated in the phase II portion. The study is expected to enrol approximately 75 adult patients in the US [2].

Evidence based evaluations

B-precursor acute lymphoblastic leukaemia (ALL) in children and young adults

Information

Licence extension / variation
Gilead Sciences
Kite

Development and Regulatory status

None
Phase II Clinical Trials
Phase II Clinical Trials
Nov 21Has breakthrough therapy status for paediatric ALL in the US [7].
Feb 20Gilead expects data read-outs in 2020 for KTE-X19 in ALL [5].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy produced ex vivo using a retroviral vector. Similar to axicabtagene but with a slightly different manufacturing process involving enrichment of lymphocytes needed for certain B-cell cancers.
Global incidence is about 3 per 100,000 population, with about 3 out of 4 cases occurring in children aged under 6 years. ALL represents 12% of all leukaemia (but 80% in children) [1].
B-precursor acute lymphoblastic leukaemia (ALL) in children and young adults
Intravenous infusion

Further information

Yes

Trial or other data

Nov 21PI/II ZUMA-4 study continues recruitment [8].
Nov 20PI/II ZUMA-4 study (previously described as only PII) is recruiting in the US, France, Canada and the netherlands, now with the aim of enrolling 116 children and young people aged up to 21 years. Collection of primary outcome data due to complete Aug 23 [6].
Jan 20No UK trial sites [4]
Apr 19Primary outcome data from PII ZUMA-4 study (NCT02625480) now expected Jul 21 [4].
Jan 18PII ZUMA-4 study (NCT02625480) is still recruiting & expects to complete collection of primary outcome data in Jun 19 [3].
Dec 15Kite Pharma initiates the pivotal PI/II ZUMA-4 study of KTE C19 in paediatric and young adult patients with relapsed or refractory acute lymphoblastic leukaemia (KTE-C19-104; NCT02625480). The phase I portion of trial is designed to assess the safety of KTE C19, and the phase II portion will assess the efficacy and safety. The trial intends to enrol approximately 75 patients in the US [2].

Evidence based evaluations

Relapsed or refractory chronic lymphocytic leukaemia (CLL) in adults

Information

Licence extension / variation
Gilead Sciences
Kite

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Apr 21KTE-X19 removed from pipeline; development discontinued [8].
Nov 20According to the company pipeline, ZUMA-8 is not considered a pivotal trial [7].
Nov 20No information found on Gilead website to explain the changes to the ZUMA-8 study and whether it significantly affects launch plans [5].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy produced ex vivo using a retroviral vector. Similar to axicabtagene but with a slightly different manufacturing process involving enrichment of lymphocytes needed for certain B-cell cancers.
CLL is the most common leukaemia in the Western world with an incidence of 4.2 per 100,000 per year. The incidence increases to >30 per 100,000 per year at an age >80 years [1].
Relapsed or refractory chronic lymphocytic leukaemia (CLL) in adults
Intravenous infusion

Trial or other data

May 21ZUMA-8 has recruited 16 patients but enrolment has now stopped, and collection of primary outcome data completed in Feb 21 [8].
Nov 20ZUMA-8 trial (now described as PI) is recruiting in the US and Italy (no UK sites) but planned enrolment has been reduced to 27; collection of primary outcome data now expected to complete Feb 22. Efficacy is no longer being assessed as a primary outcome; ORR is now a secondary outcome [4].
Jan 20No UK trial sites [3]
Nov 18PI/II ZUMA-8 study to evaluate the safety and efficacy of axicabtagene ciloleucel in patients with relapsed or refractory CLL starts (NCT03624036; KTE-C19-108). 108 patients will be recruited in the US. Primary outcome of the PI part is incidence of dose-limiting toxicities (DLTs) up to 28 days; in PII, primary outcome is objective response rate per independent review at 2 years; these data are expected to be collected by Mar 21 [2].