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36461111000001102

New Medicines

YescartaRelapsed or refractory indolent non-Hodgkin lymphoma (NHL)

Information

Yescarta
Licence extension / variation
Gilead Sciences
Kite

Development and Regulatory status

None
Phase II Clinical Trials
Launched
Yes
Yes
Jul 21Has breakthrough therapy status in US for r/r FL [11].
Mar 21Approved in US for treatment of adults with relapsed or refractory follicular lymphoma [10].
Dec 20FDA has accepted sBLA and granted Priority Review designation, with a target action date of 5/3/21. Application is based on data from PII ZUMA-5 trial [9].
Sep 20Kite has submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA for axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma after two or more prior lines of systemic therapy [6].
Apr 19Has orphan drug status in EU and US for follicular lymphoma [3].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy. T-lymphocytes are collected from the patient by leukapheresis and modified genetically ex vivo using a retroviral vector encoding an anti-CD19 CAR protein. Re-infused as a single dose.
NHL can be divided into two prognostic groups: low-grade (indolent) or high-grade (aggressive). Follicular lymphoma is an indolent form of NHL and accounts for 20-25% of all NHL. The annual incidence of follicular lymphomas has increased from 2-3 per 100,000 during the 1950s to 5-7 per 100,000 recently [1].
Relapsed or refractory indolent non-Hodgkin lymphoma (NHL)
Intravenous infusion

Further information

Yes

Trial or other data

Dec 20Primary analysis of PII ZUMA-5 trial shows high response rates in indolent non-Hodgkin lymphoma. In study (n=104), 92% of patients responded after a single infusion, including 76% achieving a complete response at a median follow-up of 17.5 months [9].
Nov 20PII ZUMA-5 trial is still recruiting; collection of primary outcome data now anticipated to finish in Feb 22 [8].
May 20Data from PII ZUMA-5 trial presented at the annual ASCO meeting. After a single infusion of Yescarta, 93% of patients (n=96 evaluable for efficacy) responded, with 80% patients achieving a complete response (CR) as assessed by an independent review committee. With a median follow-up of 15.3 months in all patients, median duration of response (DOR) was 20.8 months, median PFS was 23.5 months and median OS was not reached [7].
Apr 20Axicabtagene has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [5].
Dec 19No UK trial sites [4].
Mar 19PII ZUMA-5 trial (NCT03105336) is recruiting [2].
Jun 17PII ZUMA-5 trial to evaluate safety and efficacy of axicabtagene ciloleucel in patients with relapsed or refractory indolent non-Hodgkins lymphoma starts (KTE-C19-105; NCT03105336). The single-group assignment trial intends to enrol approximately 160 patients in the US & France. Primary outcome is objective response rate; collection of these data is due to complete Mar 20 [2].

Evidence based evaluations

YescartaDiffuse large B-cell lymphoma - second-line

Information

Yescarta
Licence extension / variation
Gilead Sciences
Kite

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Jun 21Following positive PIII trial results (ZUMA-7), Kite plan to initiate discussions later this year with the FDA, EMA and other global health authorities for a licence extension to the second-line setting for Yescarta [10].
May 20Has orphan drug status in EU [6].

Category

Autologous chimeric antigen receptor (CAR)-T cell therapy. T-lymphocytes are collected from the patient by leukapheresis and modified genetically ex vivo using a retroviral vector encoding an anti-CD19 CAR protein. Re-infused as a single dose.
12,294 people were diagnosed with non-Hodgkin’s lymphoma in the UK in 2009 (info.cancerresearchuk.org); DLBCL accounts for ~ 40% of all cases (www.macmillan.org.uk).
Diffuse large B-cell lymphoma - second-line
Intravenous infusion

Further information

Yes

Trial or other data

Jun 21Kite announced top-line results from the primary analysis of the randomised PIII global, multicentre study ZUMA-7 (n=359) showing superiority of axicabtagene ciloleucel (Yescarta) vs standard of care (SOC) in second-line relapsed or refractory large B-cell lymphoma (LBCL). With a median follow-up of two years, the study met the primary endpoint of event-free survival (EFS; hazard ratio 0.398, p <0.0001). The study also met the key secondary endpoint of objective response rate (ORR). The interim analysis of overall survival (OS) showed a trend favouring Yescarta; however, the data are immature at this time, and further analyses are planned for the future. Safety results from the study were consistent with or lower than the known safety profile of Yescarta for the treatment of LBCL in the third-line setting. 6% of patients experienced cytokine release syndrome (CRS) Grade 3 or higher, with a median onset of 3 days, and 21% experienced neurological events Grade 3 or higher. No new safety concerns were identified [10].
Oct 20PIII ZUMA-7 study has finished recruiting [7].
Apr 20Axicabtagene has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [5].
Dec 19UK Trial sites: Birmingham, Barts, UCL, Christie, Marsden [4]
Sep 18PIII ZUMA-7 study (NCT03391466) is still recruiting; timescales unchanged [3].
Dec 17PIII ZUMA-7 study (NCT03391466) to evaluate whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory DLBCL starts. 350 adults will be recruited in the US, Canada & the Netherlands. Primary outcome is event-free survival; collection of these data is due to complete Jan 22 [1].

Evidence based evaluations