Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Axicabtagene Ciloleucel · 9 trials · 16 indications
EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not.
PFS is defined as the time from randomization to disease progression or death due to any cause.
EFS:Time from randomization to disease progression (PD), best response of stable disease (SD) up to Day 150, start of new anti-lymphoma therapy including stem cell transplant, or death from any cause. PD=Score 4 (uptake moderately \> liver) or 5 (uptake markedly \> liver and/or new lesions) with increased uptake from baseline; New fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma rather than another etiology or in bone marrow; Individual node/lesion abnormal with longest diameter \> 1.5 cm, ≥ 50% increase from nadir; Splenic length increase \> 50% of prior increase beyond baseline or ≥ 2 cm increase if no prior splenomegaly; New/recurrent splenomegaly, progression of non-measurable lesions, new lesion, or new/recurrent bone marrow involvement. KM estimates was used for analysis.
CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). 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; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.
CR Rate is the percentage of participants with CR (complete metabolic response (CMR); complete radiological response (CRR)). CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). 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; and bone marrow normal by morphology.
OR:CR (complete metabolic response (CMR)+complete radiological response (CRR))+PR (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.PRR:≥50% decrease in sum of product of diameters up to 6 target 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.
Measured by the rate of TLTs and the rate of grade 3+ adverse events (AEs) regardless of attribution
DLT was defined as axicabtagene ciloleucel-related events with onset within first 30 days following infusion: * Grade (GR) 4 neutropenia lasting \> 21 days and GR 4 thrombocytopenia lasting \> 35 days from day of cell transfer; * Any axicabtagene ciloleucel-related AE requiring intubation; * All other GR 3 toxicities lasting \> 3 days and all GR 4 toxicities, with exception of following conditions which were not considered DLTs: aphasia/dysphasia or confusion/cognitive disturbance which resolved to GR ≤ 1 within 2 weeks and to baseline within 4 weeks; fever GR 3; myelosuppression defined as lymphopenia, decreased hemoglobin, neutropenia and thrombocytopenia unless neutropenia and thrombocytopenia met DLT definition described above; immediate hypersensitivity reactions occurring within 2 hours of cell infusion that were reversible to a ≤ GR 2 within 24 hours of cell administration with standard therapy; hypogammaglobulinemia GR 3 or 4.
ORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR), as assessed by the study investigators using revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007). CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; all lymph nodes and nodal masses must have regressed to normal size; spleen and/or liver must be normal size, not be palpable, and no nodules; bone marrow aspirate and biopsy must show no evidence of disease. PR: a ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of nodes, liver or spleen and no new sites of disease; multiple splenic and hepatic nodules (if present) must regress by ≥ 50% in the SPD; \> 50% decrease in the greatest transverse diameter for single nodules. 95% confidence interval (CI) was calculated by Clopper-Pearson method.
TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or continuous venovenous hemodialysis (CVVHD), and Grade 5: Death. Neurologic toxicities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.
TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.
TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.
TEAE was defined as any AE with onset on or after the start of treatment. CRS events were graded by Lee et al 2014. Grade 1 : No life threatening symptoms and require symptomatic treatment only; Grade 2: Symptoms require and respond to moderate intervention; Grade 3: Symptoms require and respond to aggressive intervention; Grade 4: Life-threatening symptoms and requirements for ventilator support or CVVHD, and Grade 5: Death. Neurologic toxicities were graded by CTCAE version 4.03. Grade 1: Mild, asymptomatic or mild symptoms and intervention not indicated; Grade 2: Moderate and minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening and urgent intervention indicated; Grade 5: Death related to AE.
| Arm | Type | Description |
|---|---|---|
| Axicabtagene Ciloleucel | 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 axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. |
| Standard of Care Therapy | ACTIVE_COMPARATOR | Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for a total of 6 cycles (21-day cycle) * Rituximab 375 mg/m\^2 on Day 1 * Cyclophosphamide 750 mg/m\^2 on Day 1 * Doxorubicin 50 mg/m\^2 on Day 1 * Vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * Prednisone 40 mg/m\^2 on Day 1 through Day 5 * Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for a total of 6 cycles (21-day cycle) * Rituximab 375 mg/m\^2 on Day 1 * Etoposide 50 mg/m\^2 on Days 1 to 4 * Doxorubicin 10 mg/m\^2 on Days 1 to 4 * Vincristine 0.4 mg/m\^2 on Days 1 to 4 * Cyclophosphamide 750 mg/m\^2 on Day 5 * Prednisone 60 mg/m\^2 twice daily on Days 1 to 5 |
| Axicabtagene Ciloleucel Treatment | EXPERIMENTAL | Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation antigen (CD) 19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. Participants who will achieve a partial response or complete response and subsequently experience disease progression may have an option to receive a second course of conditioning chemotherapy and axicabtagene ciloleucel. |
| Axicabtagene Ciloleucel and Rituximab Combination | EXPERIMENTAL | Participants will receive rituximab 375 mg/m\^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m\^2 over 30 minutes and cyclophosphamide 500 mg/m\^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m\^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133. |
| Axicabtagene Ciloleucel (Follicular Lymphoma) | EXPERIMENTAL | Participants with relapsed or refractory (r/r) B-cell indolent non-Hodgkin lymphoma (iNHL) subtype of follicular lymphoma (FL) 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 at a target dose of 2×10\^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. |
| Axicabtagene Ciloleucel (Marginal Zone Lymphoma) | EXPERIMENTAL | Participants with r/r B-cell iNHL subtype of marginal zone lymphoma (MZL) 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 IV for 3 days (Day -5 to Day -3). * A single infusion at a target dose of 2×10\^6 anti-CD19 CAR transduced autologous T cells/kg on Day 0. |
| Fludarabine + Cyclophosphamide + Axicabtagene Ciloleucel | EXPERIMENTAL | Prior to receiving axi-cel, participants will undergo leukapheresis and the need for a Ommaya reservoir placement will be assessed and administered. Day -5 to Day -3 of 28 day study cycle Fludarabine and cyclophosphamide; Day -1 admitted to hospital, receive axi-cel on day 0; Till at least cycle day 7 hospital monitoring; post treatment follow up will occur on day 14 and day 28 of cycle 1, monthly in cycles 2, 3, 6, 9,12,15,18,21,24, then yearly after cycle 24. |
| Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy | EXPERIMENTAL | Participants with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL) will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 intravenously \[IV\] over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel chimeric antigen receptor (CAR) transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight (BW) on Day 0. |
| Phase 2 (Pivotal Study): Cohort 1 | EXPERIMENTAL | Participants with refractory DLBCL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. |
| Phase 2 (Pivotal Study): Cohort 2 | EXPERIMENTAL | Participants with refractory PMBCL or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. |
| Phase 2 (Safety Management Study): Cohort 3 | EXPERIMENTAL | Participants with relapsed or refractory transplant ineligible DLBCL, PMBCL, or TFL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2 IV over 30 minutes and cyclophosphamide 500 mg/m\^2 IV over 60 minutes) on Days -5, -4, and -3; followed by a single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV twice daily (BID) starting on Day 0) and tocilizumab (8 mg/kg IV over 1 hour (not to exceed 800 mg)) on Day 2). |
| Phase 2 (Safety Management Study): Cohort 4 | EXPERIMENTAL | Participants with r/r DLBCL,PMBCL,TFL,or high-grade B-cell lymphoma(HGBCL)after 2 systemic lines of therapy will receive optional bridging therapy(dexamethasone 20mg to 40mg,eitherorally or IV daily for 1 to 4 days or 1g/m\^2 of high-dose methylprednisolone(HDMP)for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3;followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW. Participants will receive a prophylactic regimen of levetiracetam(750 mg orally or IV twice daily(BID)starting on Day 0).Participants will receive tocilizumab(initiated on persistent Grade 1 cytokine release syndrome(CRS)for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity). |
| Phase 2 (Safety Management Study): Cohort 5 | EXPERIMENTAL | Participants with r/r DLBCL, PMBCL ,TFL, or HGBCL after 2 systemic lines of therapy will receive debulking therapy (R-CHOP:rituximab 375mg/m\^2 D1,doxorubicin 50mg/m\^2 D1,prednisone 100mg D1 to D5,cyclophosphamide 750mg/m\^2 D1,vincristine 1.4 mg/m\^2 D1 or R-ICE:rituximab 375mg/ m\^2 D1,ifosfamide 5g/m\^2 24h-CI D2,carboplatin AUC5 D2 maximum dose 800mg,etoposide 100 mg/m\^2/day D1 to D3 or R-GEMOX:rituximab 375mg/m\^2 D1,gemcitabine 1000mg/m\^2 D2,oxaliplatin 100mg/m\^2 D2 or R-GDP:rituximab 375mg/m\^2 D1 or D8,gemcitabine 1g/m\^2 D1 \& D8,dexamethasone 40mg D1 to D4,cisplatin 75mg/m\^2 D1(or carboplatin AUC5 D1) or radiotherapy:20 to 30 Gy), conditioning chemotherapy (fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0. Participants will also receive a prophylactic regimen of levetiracetam (750 mg orally or IV BID starting on D0).D=Day. |
| Phase 2 (Safety Management Study): Cohort 6 | EXPERIMENTAL | Participants with r/r DLBCL,PMBCL,TFL orHGBCL after 2 systemic lines of therapy may receive bridging therapy(dexamethasone 20mg to 40mg,orally or IV daily for 1 to 4 days or 1g/m\^2 HDMP for 3 days with rituximab at 375mg/m\^2 weekly for 3 weeks or bendamustine 90 mg/m\^2 on Days 1 and 2 and rituximab 375mg/m\^2 on Day 1),conditioning chemotherapy(fludarabine 30mg/m\^2 IV and cyclophosphamide 500mg/m\^2 IV)on Days -5,-4, and -3; followed by single infusion of axicabtagene ciloleucel CAR transduced autologous T cells IV at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of BW on Day 0.Participants will also receive a prophylactic regimen of levetiracetam 750 mg orally or IV twice daily(BID)starting on Day 0)and corticosteroids(dexamethasone, 10 mg once daily on Days 0, 1, and 2).Participants will receive tocilizumab(initiated on persistent Grade 1 CRS for over 24 hours)and dexamethasone(persistent Grade 1 CRS for over 72 hours and at onset of Grade 1 neurologic toxicity). |
| Name | Type | Description |
|---|---|---|
| Axicabtagene Ciloleucel | BIOLOGICAL | A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells |
| Cyclophosphamide | DRUG | Administered intravenously |
| Fludarabine | DRUG | Administered intravenously |
| Etoposide | DRUG | Administered intravenously |
| Rituximab | DRUG | Administered intravenously |
| Doxorubicin | DRUG | Administered intravenously |
| Vincristine | DRUG | Administered intravenously |
| Prednisone | DRUG | Administered orally |
| Lenalidomide | DRUG | Administered orally |
| Bendamustine | DRUG | Administered intravenously |
| Platinum-containing Salvage Chemotherapy | DRUG | Platinum-containing salvage chemotherapy (Rituximab-ifosfamide, carboplatin, etoposide (R-ICE), Rituximab-dexamethasone, cytarabine, cisplatin,oxaliplatin (R-DHAP), Rituximab-etoposide, methylprednisolone, cisplatin, cytarabine (R-ESHAP), or Rituximab-gemcitabine, dexamethasone, cisplatin/carboplatin (R-GDP) as selected by treating investigator). |
| Dexamethasone | DRUG | Administered orally or intravenously |
| Levetiracetam | DRUG | Administered according to package insert |
| Tocilizumab | DRUG | Administered according to package insert |
| High-dose methylprednisolone | DRUG | Administered according to package insert |
| Ifosfamide | DRUG | Administered according to package insert |
| Carboplatin | DRUG | Administered according to package insert |
| Gemcitabine | DRUG | Administered according to package insert |
| Oxaliplatin | DRUG | Administered according to package insert |
| Cisplatin | DRUG | Administered according to package insert |
| Methylprednisolone | DRUG | Administered according to package insert |
Key Inclusion Criteria: * Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following: * Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) * High-grade B-cell...
Axicabtagene Ciloleucel is an investigational cell therapy being studied for the treatment of B-cell lymphomas, including relapsed/refractory follicular lymphoma, high-risk large B-cell lymphoma (LBCL), refractory diffuse large B-cell lymphoma (DLBCL), and relapsed or refractory large B-cell lymphoma. It is a monoclonal antibody-based therapy in Phase 2 clinical development.
Axicabtagene Ciloleucel is being developed by Gilead Sciences, Inc., which trades under the ticker GILD on the NASDAQ. The company is conducting clinical trials to evaluate the therapy's safety and efficacy in patients with various types of B-cell lymphoma.
Axicabtagene Ciloleucel is currently in Phase 2 clinical development. It is an investigational therapy and has not been approved by the FDA. The drug is being studied for the treatment of B-cell lymphomas, including follicular lymphoma and large B-cell lymphoma.
Axicabtagene Ciloleucel has been evaluated in several clinical trials, including NCT02348216, a Phase 1 study in refractory aggressive non-Hodgkin lymphoma; NCT03105336, a Phase 2 study in relapsed/refractory indolent non-Hodgkin lymphoma; NCT03391466, a Phase 3 study in relapsed/refractory DLBCL; and NCT03761056, a Phase 2 study in high-risk large B-cell lymphoma.
Yes, Axicabtagene Ciloleucel is also known as KTE-C19. In clinical trials, such as NCT02348216, the therapy was referred to as KTE-C19. This alternative name is used in research settings to identify the same investigational cell therapy.