Pivotal trials testing CAR-T therapy
| Trial name . | CAR-T . | Tumor type . | Population . | Primary end point . | Reported response rate (partial response or better) . |
|---|---|---|---|---|---|
| BELINDA | Tisagenlecleucel | B-cell lymphoma (not approved) | “Aggressive B-cell lymphoma that was refractory (lack of complete response) or relapsed after the receipt of a firstline anti-CD20 antibody and anthracycline-containing regimen within 12 months after the last dose. Patients had to be eligible for autologous HSCT according to the investigator’s assessment and have an ECOG performance status score of 0 or 1 (on a 5-point scale, with higher numbers indicating greater disability) and adequate organ function”19 | Event-free survival: 3.0 months vs 3.0 months (hazard ratio, 1.07; 95% CI, 0.82-1.40; P = .61) | 46% |
| KarMMa | Idecabtagene vicleucel | Multiple myeloma | “At least 3 previous regimens for multiple myeloma, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody; had disease that was refractory to their last regimen”20 | Overall response rate | 72% |
| KarMMA-3 | Idecabtagene vicleucel | Multiple myeloma | Patients “who had received 2 to 4 previous therapies including daratumumab, an immunomodulatory agent, and a proteasome inhibitor for at least 2 consecutive cycles and who had documented disease progression within 60 days after the completion (last dose) of the last therapy”21 | Progression-free survival | 71% |
| TRANSCEND | Lisocabtagene maraleucel | Large B-cell lymphoma | “PET-positive relapsed or refractory diffuse large B-cell lymphoma (de novo or transformed from any indolent lymphoma), high-grade B-cell lymphoma with rearrangements in MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), primary mediastinal B-cell lymphoma, or follicular lymphoma grade 3B. Patients must have received 2 or more previous lines of systemic treatment (including previous chemoimmunotherapy containing anti-CD20 and anthracycline) with subsequent relapse, and they could have received a previous autologous or allogeneic hematopoietic stem-cell transplant”22 | Objective response rate | 73% |
| TRANSFORM | Lisocabtagene maraleucel | Large B-cell lymphoma | “Large B-cell lymphoma refractory to or relapsed within 12 months after initial response to firstline therapy including an anthracycline and an anti-CD20 monoclonal antibody, Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, and PET-positive disease per Lugano 2014 criteria before randomization”23 | Event-free survival: 10.1 months vs 2.3 months (hazard ratio, 0.35; 95% CI, 0.23-0.53) | 86% |
| PILOT | Lisocabtagene maraleucel | Large B-cell lymphoma | “Relapsed or refractory large B-cell lymphoma and PET-positive disease, had received firstline therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician”24 | Overall response rate | 80% |
| ELARA | Tisagenlecleucel | Follicular lymphoma | “Follicular lymphoma (grade 1, 2, or 3A) and meet one of the following criteria: (1) refractory to a second or later line of systemic therapy (including an anti-CD20 antibody and an alkylating agent) or relapsed within 6 months after completion of a second or later line of systemic therapy; (2) relapsed during anti-CD20 antibody maintenance (following at least 2 lines of therapies as above) or within 6 months after maintenance completion; and (3) relapsed after autologous HSCT”25 | Complete response rate | 86% |
| JULIET | Tisagenlecleucel | Large B-cell lymphoma | “Relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation”26 | Overall response | 50% |
| ELIANA | Tisagenlecleucel | B-cell ALL | “Children and young adults with relapsed or refractory B-cell ALL”27 | Overall remission rate | 83% |
| ZUMA-1 | Axicabtagene ciloleucel | Large B-cell lymphoma | “Diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy”28 | Objective response rate | 72% |
| ZUMA-2 | Brexucabtagene autoleucel | Mantle cell lymphoma | “Relapsed or refractory mantle cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to 5 previous therapies; all patients had to have received BTK inhibitor therapy previously”29 | Objective response rate | 87% |
| ZUMA-3 | Brexucabtagene autoleucel | B-cell ALL | “Eastern Cooperative Oncology Group performance status of 0–1 and had relapsed or refractory B-precursor acute lymphoblastic leukemia with morphological disease in the bone marrow (>5% blasts) at study entry. Relapsed or refractory disease was defined as primary refractory, first relapse with remission of 12 months or less, relapsed or refractory after at least 2 previous lines of systemic therapy, or relapsed or refractory after allo-SCT”30 | Overall complete remission or complete remission with incomplete hematological recovery | 65% |
| ZUMA-5 | Axicabtagene ciloleucel | Follicular lymphoma | “Histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had 2 or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1”31 | Overall response rate | 91% |
| ZUMA-7 | Axicabtagene ciloleucel | Large B-cell lymphoma | “Large B-cell lymphoma that was refractory to firstline treatment or that had relapsed from complete remission no more than 12 months after the completion of firstline chemoimmunotherapy including an anti-CD20 monoclonal antibody and anthracycline-containing regimen; patients intended to proceed to high-dose chemotherapy with autologous stem-cell transplantation”32 | Event-free survival: 8.3 months vs 2.0 months (hazard ratio, 0.40; 95% CI, 0.31-0.51; P < .001) | 83% |
| CARTITUDE-1 | Ciltacabtagene autoleucel | Multiple myeloma | “Multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody”33 | Overall response rate | 98% |
| CARTITUDE-4 | Ciltacabtagene autoleucel | Multiple myeloma | Patients with lenalidomide resistance “and had received 1 to 3 lines of therapy, including a proteasome inhibitor and an immunomodulatory drug”34 | Progression-free survival | 85% |
| Trial name . | CAR-T . | Tumor type . | Population . | Primary end point . | Reported response rate (partial response or better) . |
|---|---|---|---|---|---|
| BELINDA | Tisagenlecleucel | B-cell lymphoma (not approved) | “Aggressive B-cell lymphoma that was refractory (lack of complete response) or relapsed after the receipt of a firstline anti-CD20 antibody and anthracycline-containing regimen within 12 months after the last dose. Patients had to be eligible for autologous HSCT according to the investigator’s assessment and have an ECOG performance status score of 0 or 1 (on a 5-point scale, with higher numbers indicating greater disability) and adequate organ function”19 | Event-free survival: 3.0 months vs 3.0 months (hazard ratio, 1.07; 95% CI, 0.82-1.40; P = .61) | 46% |
| KarMMa | Idecabtagene vicleucel | Multiple myeloma | “At least 3 previous regimens for multiple myeloma, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody; had disease that was refractory to their last regimen”20 | Overall response rate | 72% |
| KarMMA-3 | Idecabtagene vicleucel | Multiple myeloma | Patients “who had received 2 to 4 previous therapies including daratumumab, an immunomodulatory agent, and a proteasome inhibitor for at least 2 consecutive cycles and who had documented disease progression within 60 days after the completion (last dose) of the last therapy”21 | Progression-free survival | 71% |
| TRANSCEND | Lisocabtagene maraleucel | Large B-cell lymphoma | “PET-positive relapsed or refractory diffuse large B-cell lymphoma (de novo or transformed from any indolent lymphoma), high-grade B-cell lymphoma with rearrangements in MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), primary mediastinal B-cell lymphoma, or follicular lymphoma grade 3B. Patients must have received 2 or more previous lines of systemic treatment (including previous chemoimmunotherapy containing anti-CD20 and anthracycline) with subsequent relapse, and they could have received a previous autologous or allogeneic hematopoietic stem-cell transplant”22 | Objective response rate | 73% |
| TRANSFORM | Lisocabtagene maraleucel | Large B-cell lymphoma | “Large B-cell lymphoma refractory to or relapsed within 12 months after initial response to firstline therapy including an anthracycline and an anti-CD20 monoclonal antibody, Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, and PET-positive disease per Lugano 2014 criteria before randomization”23 | Event-free survival: 10.1 months vs 2.3 months (hazard ratio, 0.35; 95% CI, 0.23-0.53) | 86% |
| PILOT | Lisocabtagene maraleucel | Large B-cell lymphoma | “Relapsed or refractory large B-cell lymphoma and PET-positive disease, had received firstline therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician”24 | Overall response rate | 80% |
| ELARA | Tisagenlecleucel | Follicular lymphoma | “Follicular lymphoma (grade 1, 2, or 3A) and meet one of the following criteria: (1) refractory to a second or later line of systemic therapy (including an anti-CD20 antibody and an alkylating agent) or relapsed within 6 months after completion of a second or later line of systemic therapy; (2) relapsed during anti-CD20 antibody maintenance (following at least 2 lines of therapies as above) or within 6 months after maintenance completion; and (3) relapsed after autologous HSCT”25 | Complete response rate | 86% |
| JULIET | Tisagenlecleucel | Large B-cell lymphoma | “Relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation”26 | Overall response | 50% |
| ELIANA | Tisagenlecleucel | B-cell ALL | “Children and young adults with relapsed or refractory B-cell ALL”27 | Overall remission rate | 83% |
| ZUMA-1 | Axicabtagene ciloleucel | Large B-cell lymphoma | “Diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy”28 | Objective response rate | 72% |
| ZUMA-2 | Brexucabtagene autoleucel | Mantle cell lymphoma | “Relapsed or refractory mantle cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to 5 previous therapies; all patients had to have received BTK inhibitor therapy previously”29 | Objective response rate | 87% |
| ZUMA-3 | Brexucabtagene autoleucel | B-cell ALL | “Eastern Cooperative Oncology Group performance status of 0–1 and had relapsed or refractory B-precursor acute lymphoblastic leukemia with morphological disease in the bone marrow (>5% blasts) at study entry. Relapsed or refractory disease was defined as primary refractory, first relapse with remission of 12 months or less, relapsed or refractory after at least 2 previous lines of systemic therapy, or relapsed or refractory after allo-SCT”30 | Overall complete remission or complete remission with incomplete hematological recovery | 65% |
| ZUMA-5 | Axicabtagene ciloleucel | Follicular lymphoma | “Histologically confirmed indolent non-Hodgkin lymphoma (follicular lymphoma or marginal zone lymphoma), had relapsed or refractory disease, previously had 2 or more lines of therapy (including an anti-CD20 monoclonal antibody with an alkylating agent), and an Eastern Cooperative Oncology Group performance score of 0 or 1”31 | Overall response rate | 91% |
| ZUMA-7 | Axicabtagene ciloleucel | Large B-cell lymphoma | “Large B-cell lymphoma that was refractory to firstline treatment or that had relapsed from complete remission no more than 12 months after the completion of firstline chemoimmunotherapy including an anti-CD20 monoclonal antibody and anthracycline-containing regimen; patients intended to proceed to high-dose chemotherapy with autologous stem-cell transplantation”32 | Event-free survival: 8.3 months vs 2.0 months (hazard ratio, 0.40; 95% CI, 0.31-0.51; P < .001) | 83% |
| CARTITUDE-1 | Ciltacabtagene autoleucel | Multiple myeloma | “Multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody”33 | Overall response rate | 98% |
| CARTITUDE-4 | Ciltacabtagene autoleucel | Multiple myeloma | Patients with lenalidomide resistance “and had received 1 to 3 lines of therapy, including a proteasome inhibitor and an immunomodulatory drug”34 | Progression-free survival | 85% |
ALL, acute lymphoblastic leukemia; allo-SCT, allogeneic stem cell transplantation; BTK, Bruton tyrosine kinase; ECOG, Eastern Cooperative Oncology Group; HSCT, hematopoietic stem cell transplantation; PET, positron emission tomography.