Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Liso-cel, JCAR017 (lisocabtagene maraleucel), JCAR017, Breyanzi®, BMS-986387
Lisocabtagene maraleucel · 10 trials · 24 indications
Time from randomization to death, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR) by 9 weeks or start of new antineoplastic therapy, whichever occurs first. CR: Target nodes masses must regress to ≤ 1.5cm in LDi, no extralymphatic sites, no new lesions. PR: ≥ 50% decrease in sum of diameters of up to 6 target nodes and extranodal sites, no new lesions, spleen must have regressed \> 50% in length. PD: LDi \> 1.5cm, increase by ≥ 50% from PPD nadir, an increase in LDi or SDi from nadir, 0.5 cm for lesions ≤ 2cm, 1.0cm for lesions \> 2cm. Complete metabolic response: Lymph nodes score 1, 2, 3 with/without residual mass on 5-point scale, no new lesions, no FDG-avid disease. Partial metabolic response: Lymph nodes score 4 or 5, reduced uptake from baseline, no new lesions, residual uptake higher than normal, reduced from baseline. Progressive metabolic disease: Score 4 or 5 with an increase in uptake intensity from baseline and/or new FDG-avid.
The complete response rate (CRR) is defined as the proportion of subjects achieving an objective response of complete response prior to start of another non-study anticancer therapy. CRR is based on the best overall response post-lisocabtagene maraleucel infusion. CRR will be defined according to the Lugano Classification.
Defined as the time from the date of liso-cel infusion to the date of first documented disease relapse or progression as assessed by the investigator, or death from any cause, whichever occurs first
Is defined as the percentage of participants achieving either a partial response (PR) or complete response (CR) at any time up to 60 months after JCAR017 treatment as assessed by PET-CT and/or CT using "The Lugano classification"
Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).
NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity. Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.
Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.
Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.
Overall response rate (ORR) by Independent Review Committee (Cohorts 1, 2, 3). ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: No * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: No * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: No * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall response rate (ORR) is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: None * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: None/normal * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall response rate (ORR) determined by Investigator assessment after JCAR017 infusion. The ORR is the percent of participants with best overall response (BOR) of either complete response (CR), complete response unconfirmed (Cru) or partial response (PR). Complete response (CR): * Brain imaging: No contrast enhancement * Corticosteroid dose: None * Eye examination: Normal * Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu): * Brain imaging: No contrast enhancement, Minimal abnormality * Corticosteroid dose: Any * Eye examination: Normal, minor RPE abnormality * Cerebrospinal fluid cytology: Negative Partial response (PR): * Brain imaging: 50% decrease in enhancing tumor, no contrast enhancement. * Corticosteroid dose: Irrelevant * Eye examination: Minor RPE abnormality, decrease in vitreous cells or retinal infiltrate. * Cerebrospinal fluid cytology: Negative, persistent or suspicious
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: * Results in death; * Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); * Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). * Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions); * Is a congenital anomaly/birth defect; * Constitutes an important medical event. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (\>70% vs \<70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy.
Participants enrolled in Phase 1 are considered evaluable for DLTs if they received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and completed the specified DLT evaluation period or if they have received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and experience a DLT during the DLT evaluation period.
Percentage of participants achieving a complete response (CR). CR is complete radiologic response (CRR) and complete metabolic response (CMR). CR was measured using CT and PET and assessed for the presence of index and non-index lesions, spleen size, and the absence of new lesions or diseased bone marrow. To be considered as having CRR participants had to have all of the following: * Index lesions - longest transverse diameter of nodal lesions ≤ 1.5 cm and the absence of extranodal disease. * Non-index lesions - the absence of non-index lesions. * Spleen size \<13 cm * The absence of new lesions * Normal bone marrow assessment To be considered as having CMR participants had to have all of the following: * A score of 1, 2, or 3 with or without residual mass on 5-PS for index and non-index lesions. * The absence of new lesions * No evidence of FDG-avid disease in marrow and a normal bone marrow assessment
Proportion of subjects experiencing adverse events
Proportion of subjects experiencing laboratory abnormalities
Proportion of subjects experiencing adverse events
Proportion of subjects experiencing laboratory abnormalities
Proportion of subjects who have CR after treatment with JCAR017 + ibrutinib using iwCLL 2018 guidelines
Proportion of subjects experiencing adverse events
Proportion of subjects experiencing laboratory abnormalities
Proportion of subjects who have CR after treatment with JCAR017 + venetoclax using iwCLL 2018 guidelines
Proportion of subjects who have CR after treatment with JCAR017 using iwCLL 2018 guidelines
ORR defined as the rate of complete response/remission (CR) \[including complete response/remission with incomplete marrow recovery (Cri)\] plus PR \[including nodular partial response (nPR)\] based on Independent Review Committee (IRC) assessment using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines
| Arm | Type | Description |
|---|---|---|
| Arm A - Standard of Care (SOC) | ACTIVE_COMPARATOR | Subjects should receive SOC (R-DHAP, R-ICE or R-GDP) followed by HDCT (BEAM) and HSCT. Standard of care regimen will be administered as per investigator decision. |
| Arm B - JCAR017 | EXPERIMENTAL | Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently followed by JCAR017 infusion. |
| Liso-Cel after Glofit-GemOx bridging therapy | EXPERIMENTAL | Participants will receive obinutuzumab at the pre-determined dose 4 days prior to undergoing leukapheresis. After leukapheresis, participants will receive glofitamab, gemcitabine, and oxaliplatin (Glofit-GemOx) at the pre-determined doses over 3 weeks for 1-2 treatment cycles (each cycle is 21 days). Participants will then receive lymphodepleting chemotherapy of fludarabine and cyclophosphamide at the pre-determined doses for 3 consecutive days. Lsiocabtagene maraleucel (liso-cel) will be administered 2-7 days after the participants completes lymphodepleting chemotherapy. |
| Liso-cel Administration | EXPERIMENTAL | - |
| Administration of JCAR017 | EXPERIMENTAL | * Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) and cyclophosphamide IV (300 mg/m2/day for 3 days) prior to JCAR017 infusion. Refer to the most recent package inserts for further details on administration of these agents. * JCAR017 will be infused on Day 1 at a target dose of 100 × 10\^6 CAR-positive viable T cells (CAR+ T cells), 2 to 7 days after completion of LD chemotherapy. Each JCAR017 dose includes CD4+ CAR+ T cells and CD8+ CAR+ T cells. |
| Lisocabtagene maraleucel | EXPERIMENTAL | Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection. |
| Treatment | EXPERIMENTAL | Lisocabtagene maraleucel at a dose of 100×10\^6 CAR+ T cells (50×10\^6 CD8+ CAR+ T cells and 50×10\^6 CD4+ CAR+ T cells), will be given IV in a single-dose schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy). |
| Single arm | EXPERIMENTAL | Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation. |
| Arm A: JCAR017 in combination with Durvalumab | EXPERIMENTAL | JCAR017 will be administered at a single flat dose of 50 x 10\^6 CAR+T cells or 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules |
| Arm B: JCAR017 in combination with CC-122 | EXPERIMENTAL | This arm will test JCAR017 in combination with the CC-122. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses |
| Arm C: JCAR017 in combination with CC-220 | EXPERIMENTAL | This arm will test JCAR017 in combination with CC-220. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses |
| Arm D: JCAR017 in combination with Ibrutinib | EXPERIMENTAL | This arm will test JCAR017 in combination with ibrutinib. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at a fixed dose of 420 mg daily |
| Arm E: JCAR017 in combination with relatlimab and/or nivolumab | EXPERIMENTAL | This arm will test JCAR017 in combination with relatlimab and/or nivolumab in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules |
| Arm F: JCAR017 in combination with CC-99282 | EXPERIMENTAL | This arm will test JCAR017 in combination with CC-99282 in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules. |
| Phase 1 JCAR017 monotherapy | EXPERIMENTAL | Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel) |
| Phase 1 JCAR017 + ibrutinib | EXPERIMENTAL | Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm + ibrutinib |
| Phase 2 JCAR017 monotherapy | EXPERIMENTAL | Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm |
| Phase 1 JCAR017 + venetoclax | EXPERIMENTAL | Subjects will receive venetoclax as bridging anticancer therapy until lymphodepletion chemotherapy/ JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm. After JCAR017 infusion subjects will receive venetoclax until Day 90. |
| Phase 2 JCAR017 Double-Exposed Monotherapy Expansion (DEME) | EXPERIMENTAL | Subjects will receive JCAR017 monotherapy |
| Name | Type | Description |
|---|---|---|
| Standard of Care | DRUG | Standard of Care |
| JCAR017 | GENETIC | JCAR017 |
| Obinutuzumab | DRUG | Intravenous infusion received once, 5 days prior to receiving the first doses of glotfitamab, gemcitabine, and oxaliplatin. |
| Glofitamab | DRUG | Intravenous infusion received on days 1, 3, 8, and 15 of cycle 1 and on day 15 of the optional cycle 2 (each cycle is 21 days). |
| Gemcitabine & oxaliplatin | DRUG | Intravenous infusions received on day 1 of cycle 1 and an optional cycle 2 (each cycle is 21 days). |
| Leukapheresis | PROCEDURE | Procedure to collect stem cells for modification that will occur 2 days prior to administration of the first doses of glofitamab, gemcitabine, and oxaliplatin. |
| Lymphodepleting chemotherapy | DRUG | Intravenous infusions of cyclophosphamide and fludarabine administered for 3 consecutive days 3-5 days prior to receive lisocabtagene maraleucel. |
| LISOCABTAGENE MARALEUCEL | DRUG | Intravenous infusion of participant's re-manufactured stem cells administered one 3-5 days after completing lymphodepleting chemotherapy. |
| Rituximab | DRUG | Specified dose on specified days |
| Methotrexate | DRUG | Specified dose on specified days |
| Procarbazine | DRUG | Specified dose on specified days |
| Temozolomide | DRUG | Specified dose on specified days |
| Liso-cel | BIOLOGICAL | Specified dose on specified days |
| Fludarabine | DRUG | Specified dose on specified days |
| Cyclophosphamide | DRUG | Specified dose on specified days |
| Calcium folinate | DRUG | Specified dose on specified days |
| Bridging radiation therapy | RADIATION | Days -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received. |
| Post-infusion radiation | RADIATION | Days 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy. |
| Durvalumab | DRUG | Anti-PD-L1 |
| CC-122 | DRUG | Pleiotropic Pathway Modifier |
| Ibrutinib | DRUG | Ibrutinib |
| CC-220 | DRUG | CC-220 |
| Relatlimab | DRUG | Relatlimab |
| Nivolumab | DRUG | Nivolumab |
| CC-99282 | DRUG | CC-99282 |
| JCAR017 (lisocabtagene maraleucel) | BIOLOGICAL | Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging anticancer therapy for disease control. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection. |
| JCAR017 (lisocabtagene maraleucel) + ibrutinib | BIOLOGICAL | Participants eligible for this cohort should be receiving ibrutinib at the time of screening. For participants who previously discontinued ibrutinib, ibrutinib will be started as soon as possible after eligibility is confirmed. Ibrutinib treatment will continue for up to 90 days after JCAR017 infusion (or longer for participants who are receiving benefit from ibrutinib). Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection. |
| JCAR017 (lisocabtagene maraleucel) + venetoclax | BIOLOGICAL | Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants will receive venetoclax as bridging anticancer therapy on a weekly ramp up dosing schedule until stopping one day prior to lymphodepletion. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection, and the day after infusion venetoclax will be re-initiated. |
Inclusion Criteria: 1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF). 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), h...
Lisocabtagene maraleucel is a CAR-T cell therapy being developed by Bristol-Myers Squibb Company (ticker BMY). It is an investigational treatment in clinical development for blood cancers, including diffuse large B cell lymphoma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. It is given as a cell-based therapy rather than as a conventional small molecule or antibody drug.
Lisocabtagene maraleucel is being studied for several B cell blood cancers: diffuse large B cell lymphoma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, including relapsed or refractory large B cell lymphoma and primary central nervous system lymphoma. These uses are investigational and are being evaluated in clinical trials rather than as established approved indications.
Lisocabtagene maraleucel targets CD19, a protein found on the surface of B cells. It is a CAR-T therapy, meaning the patient's T cells are engineered to recognize and bind CD19, directing an immune response against CD19-positive B cells. CD19 is a binding agent target class in this program.
Lisocabtagene maraleucel is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The program has also been known by the code JCAR017 during its development. Bristol-Myers Squibb is the sponsor behind the clinical trials evaluating the therapy across B cell malignancies.
Lisocabtagene maraleucel is in clinical development and is investigational. Its trials span Phase 1 and Phase 2, with six studies in total, of which one is active and five are completed. It has not been established as an approved therapy in the indications described here.
Lisocabtagene maraleucel has been studied in trials including NCT04245839, a Phase 2 study in relapsed or refractory indolent B cell non-Hodgkin lymphoma, and NCT05621096, a Phase 1 study of low dose radiation as bridging therapy in relapsed B cell non-Hodgkin lymphoma. Current studies include NCT07015242 in primary central nervous system lymphoma and NCT07711483, the GLORY trial.
Yes. Lisocabtagene maraleucel is also known as liso-cel and by the development code JCAR017. These names refer to the same CD19-directed CAR-T cell therapy developed by Bristol-Myers Squibb. Searches for JCAR017 or liso-cel refer to this same investigational product.