Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Tecartus, Brexucabtagene Autoleucel
KTE-X19 · 6 trials · 5 indications
ORR is defined as the incidence of a complete remission (CR) or a partial remission (PR) per the Lugano Classification.
OCR rate is defined as the percentage of participants achieving CR/complete remission with incomplete hematologic recovery (CRi) per investigator assessment.
The primary endpoint is RFS, defined as the time from KTE-X19 infusion until clinical relapse or death from any cause. Patients proceeding to subsequent anti-cancer therapy, inclusive of allogeneic transplantation, without relapse will be censored in this analysis. Surviving patients not meeting criteria for relapse by the analysis data cutoff date will be censored at their last evaluable disease assessment date.
OR: complete metabolic response (CMR),complete radiological response (CRR), partial MR response (PMR),partial RR(PRR).CMR:score 1(no uptake above background)/2(uptake ≤mediastinum)/3(uptake \>mediastinum but ≤liver) with/without a residual mass on positron emission tomography 5-point scale;no new lesions.CRR:target nodes/nodal masses regressed to ≤1.5cm in longest transverse diameter of lesion (LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal;no new sites;bone marrow normal by morphology. PMR:score 4(uptake moderately \>liver)/5(uptake markedly \>liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥50% decrease in sum of the product of the diameters(SPD) of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by \>50% in length beyond normal.
OR: complete metabolic response(CMR),complete radiological response(CRR),partial MR response(PMR),partial RR(PRR).CMR:score 1(no uptake above background)/2(uptake ≤ mediastinum)/3(uptake \> mediastinum but ≤ liver)with/without a residual mass on positron emission tomography 5-point scale;no new lesions.CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion(LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal;no new sites;bone marrow normal by morphology. PMR:score 4(uptake moderately \> liver)/5(uptake markedly \> liver, new lesions)with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT).PRR: ≥ 50% decrease in sum of the product of the diameters(SPD)of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by \> 50% in length beyond normal.
OR: CMR, CRR, PMR, PRR. CMR: score 1(no uptake above background) / 2(uptake ≤ mediastinum) / 3(uptake \> mediastinum but ≤ liver) with/without a residual mass on positron emission tomography 5-point scale; no new lesions. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in LDi; no extralymphatic sites of disease;absent non-measured lesion NMLs; organ enlargement regress to normal; no new sites; bone marrow normal by morphology. PMR: score 4(uptake moderately \> liver) /5 (uptake markedly \> liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at EOT. PRR: ≥ 50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by \> 50% in length beyond normal. Percentages were rounded off.
DLT is drug-related events with onset within first 28 days following infusion: * Grade (GR) 4 hematologic toxicity lasting more than 30 days (except lymphopenia) if not attributable to underlying disease * All drug-related GR 3 lasting for \> 7 days or 4 non-hematologic toxicities regardless of duration (except: aphasia/dysphasia or confusion/cognitive disturbance which resolves to at least GR 1/baseline within 2 weeks or baseline within 4 weeks, fever GR 3/ 4, immediate hypersensitivity reactions within 2 hours of drug infusion that are reversible ≤ GR 2 within 24 hours, renal toxicity which requires dialysis for ≤ 7 days, intubation for airway protection if ≤ 7 days, tumor lysis syndrome, GR 3 liver function test elevation, provided there is resolution to ≤ GR 2 within 14 days, GR 4 transient serum hepatic enzyme abnormalities provided there is resolution to ≤ GR 3 within \< 72 hours, hypogammaglobulinemia GR 3/ 4 and GR 3 nausea and/or anorexia).
OCR rate:percentage of participants achieving CR+CRi.CR: ≤5% blasts by morphology in bone marrow(BM);absolute neutrophil count(ANC)≥1000/microliters (μL) and platelets(Plt) ≥100000/μL in peripheral blood(PB);central nervous system extramedullary disease(CNS EMD) of CNS-1(no detectable leukemia in cerebrospinal fluid\[CSF\]);Non-CNS baselineEMD:if present(images shows CR),if no(images not needed),if performed shows negative positron emission tomography(PET) baseline,baseline lesions shows CR as disappearance of measurable and nonmeasurable nodal lesions(Nodal masses \>1.5 cm in greatest transverse diameter\[GTD\] at baseline have regressed to ≤l.5 cm GTD,nodes that were 1.1 to 1.5 cm\[long axis\] and \>1.0 cm\[short axis\] have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions.CRi:all CR criteria except in PB ANC≥1000/μL and Plt\<100000/μL or ANC\<1000/μL and Plt ≥100000/μL.95% confidence interval (CI) was calculated by Clopper-Pearson method.
Dose-limiting toxicity is defined as protocol-defined brexucabtagene autoleucel (KTE-X19)-related events with onset within the first 28 days following brexucabtagene autoleucel (KTE-X19) infusion.
Overall complete remission rate will be determined per independent review.
Objective Response Rate will be determined per investigator review.
| Arm | Type | Description |
|---|---|---|
| MCL Cohort- KTE-X19 | EXPERIMENTAL | Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells will be administered. |
| ALL Cohort- KTE-X19 | EXPERIMENTAL | Participants will receive cyclophosphamide 900 mg/m\^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m\^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10\^6 19 CAR T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells will be administered. |
| Autologous CAR T-cell immunotherapy | EXPERIMENTAL | Tecartus will be delivered at a target dose of 1x106 cells / kg. For those \>100 kg, a flat dose of 1 x108 cells will be used. Tecartus will be administered on day 0, following 1 day of rest from conditioning chemotherapy. |
| Brexucabtagene autoleucel (KTE-X19) | EXPERIMENTAL | Participants with relapsed or refractory (r/r) mantle cell lymphoma (MCL) who have been treated with up to 5 prior regimens but have not received prior therapy with a Bruton's tyrosine kinase inhibitor (BTKi) will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day for 3 days (Day -5 to Day -3). * A single infusion of brexucabtagene autoleucel at a target dose of 2×10\^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg, with a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells for participants \> 100 kg on Day 0. |
| Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19) | EXPERIMENTAL | Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10\^6 CAR T cells/kg, with a maximum dose of 2 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10\^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2. |
| Phase 1: 2 x 10^6 Anti-CD19 CAR T Cells/kg | EXPERIMENTAL | Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 intravenously \[IV\] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. |
| Phase 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg | EXPERIMENTAL | Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. |
| Phase 1: 0.5 x 10^6 Anti-CD19 CAR T Cells/kg | EXPERIMENTAL | Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 0.5 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 0.5 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. |
| Phase 2: 1 x 10^6 Anti-CD19 CAR T Cells/kg | EXPERIMENTAL | Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. |
| Single Arm | EXPERIMENTAL | A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of chimeric antigen receptor (CAR) transduced autologous T cells administered intravenously at a target dose of 2 x 10\^6 anti-CD19 CAR+ T cells/kg or 1 x 10\^6 anti-CD19 CAR+ T cells/kg. |
| Name | Type | Description |
|---|---|---|
| KTE-X19 | DRUG | A single infusion of chimeric antigen receptor (CAR) T cells |
| Cyclophosphamide | DRUG | Administered intravenously |
| Fludarabine | DRUG | Administered intravenously |
| Tecartus | DRUG | Tecartus is a CD19 directed CAR T-cell therapy that utilizes CD28 costimulatory and CD3 zeta stimulatory domains. Tecartus is manufactured from purified autologous T-cells via retroviral transduction with a median time to product release of 13 days. |
| Brexucabtagene autoleucel | BIOLOGICAL | Administered as intravenous infusion |
| Axicabtagene Ciloleucel | DRUG | A single infusion of axicabtagene ciloleucel anti-CD 19 CAR T cells |
| Brexucabtagene Autoleucel (KTE-X19) | BIOLOGICAL | - |
Key Inclusion Criteria: MCL Cohort: * Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or presence of t(11;14) * Up to 5 prior regimens for MCL. Prior therapy must have included: * Anthracycline-, bendamustine-, or high-dose cytarabine- containing chemother...
KTE-X19 is an investigational cell therapy being developed by Gilead Sciences, Inc. for relapsed or refractory mantle cell lymphoma and relapsed or refractory B-precursor acute lymphoblastic leukemia. It is currently in Phase 2 clinical development and has not been approved by the FDA.
KTE-X19 is being studied for the treatment of relapsed or refractory mantle cell lymphoma and relapsed or refractory B-precursor acute lymphoblastic leukemia in adult patients. These are cancers of the blood and lymphatic system that have returned or stopped responding to prior therapy.
KTE-X19 is being developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead is the sponsor of the clinical program evaluating the therapy in relapsed or refractory mantle cell lymphoma and B-precursor acute lymphoblastic leukemia.
KTE-X19 is in Phase 2 clinical development. It is an investigational therapy and has not been approved by the FDA for any indication. The ongoing Phase 2 study is evaluating it in adult patients with relapsed or refractory mantle cell lymphoma or relapsed or refractory B-precursor acute lymphoblastic leukemia.
KTE-X19 is being evaluated in one active Phase 2 trial, NCT06253663, titled Study of KTE-X19 in Adult Japanese Participants With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia. The trial is active but not recruiting, has an estimated enrollment of 25 participants, and is being conducted in Japan.