UPDATED RESULTS FROM ZUMA-1: A PHASE 1-2 MULTICENTER STUDY EVALUATING THE SAFETY AND EFFICACY OF KTE-C19 (ANTI-CD19 CAR T CELLS) IN REFRACTORY AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA (NHL)
(Abstract release date: 05/19/16)
EHA Library. Siddiqi T. 06/12/16; 135285; S791
Ms. Tanya Siddiqi
Contributions
Contributions
Abstract
Abstract: S791
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most prevalent hematologic malignancy in the US and the 5th most deadly cancer with nearly 19,790 deaths/year. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, representing 25-35% of new cases annually. Approximately 1 in 3 patients treated in the first line will be refractory to treatment or relapse post-treatment and represent a significant unmet medical need. Patients with relapsed/refractory B-cell malignancies demonstrated durable remissions when treated with CD28/CD3zeta anti-CD19 CAR T cells at the National Cancer Institute (NCI) (Kochenderfer, JCO 2015; NCT00924326). KTE-C19 includes the same CAR construct as that used in the NCI trial, but is centrally manufactured in a streamlined 6- to 8-day process. Updated data from the phase 1 portion of the ZUMA-1 clinical trial are reported.
Aims
The primary goal was to determine the safety of KTE-C19. Secondary aims included evaluation of overall response rate, duration of response, blood concentrations of CAR T cells, and serum cytokine levels.
Methods
Patients with relapsed/refractory aggressive B-cell NHL were treated with a single target dose of 2 × 106 anti-CD19 CAR T cells (KTE-C19)/kg following a fixed dose of cyclophosphamide/fludarabine conditioning chemotherapy. Key inclusion criteria were ECOG 0-1 and chemo-refractory disease, which was defined as progressive or stable disease as best response to last line of therapy or disease progression ≤ 12 months after autologous stem cell transplantation. All patients provided informed consent.
Results
Seven patients received KTE-C19 as of January 15, 2016. A previously reported dose-limiting toxicity of grade 4 cytokine release syndrome and neurotoxicity occurred in one patient. All other grade ≥ 2 cytokine release syndrome and neurotoxicity adverse events resolved within one month. There were no other adverse events due to KTE-C19 after one month post-dosing. The overall response rate was 71%, with a complete response rate of 57%. Ongoing complete responses of 3 to 6+ months were present in 3 patients who previously demonstrated disease progression within 6 months of autologous stem cell transplantation. Levels of CAR T cells peaked within 2 weeks and remained detectable 1 to 6+ months after infusion. Updated results will be presented.
Conclusion
Additional follow up of patients enrolled in the ZUMA-1 trial demonstrated durable complete remissions after a single dose of KTE-C19, with no new KTE-C19-related adverse events. The KTE-C19 regimen and central, streamlined manufacturing process were safe and feasible for future studies. The phase 2 portion of the ZUMA-1 clinical trial (NCT02348216) is ongoing.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemorefractory, Immunotherapy, Lymphoma, T cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most prevalent hematologic malignancy in the US and the 5th most deadly cancer with nearly 19,790 deaths/year. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, representing 25-35% of new cases annually. Approximately 1 in 3 patients treated in the first line will be refractory to treatment or relapse post-treatment and represent a significant unmet medical need. Patients with relapsed/refractory B-cell malignancies demonstrated durable remissions when treated with CD28/CD3zeta anti-CD19 CAR T cells at the National Cancer Institute (NCI) (Kochenderfer, JCO 2015; NCT00924326). KTE-C19 includes the same CAR construct as that used in the NCI trial, but is centrally manufactured in a streamlined 6- to 8-day process. Updated data from the phase 1 portion of the ZUMA-1 clinical trial are reported.
Aims
The primary goal was to determine the safety of KTE-C19. Secondary aims included evaluation of overall response rate, duration of response, blood concentrations of CAR T cells, and serum cytokine levels.
Methods
Patients with relapsed/refractory aggressive B-cell NHL were treated with a single target dose of 2 × 106 anti-CD19 CAR T cells (KTE-C19)/kg following a fixed dose of cyclophosphamide/fludarabine conditioning chemotherapy. Key inclusion criteria were ECOG 0-1 and chemo-refractory disease, which was defined as progressive or stable disease as best response to last line of therapy or disease progression ≤ 12 months after autologous stem cell transplantation. All patients provided informed consent.
Results
Seven patients received KTE-C19 as of January 15, 2016. A previously reported dose-limiting toxicity of grade 4 cytokine release syndrome and neurotoxicity occurred in one patient. All other grade ≥ 2 cytokine release syndrome and neurotoxicity adverse events resolved within one month. There were no other adverse events due to KTE-C19 after one month post-dosing. The overall response rate was 71%, with a complete response rate of 57%. Ongoing complete responses of 3 to 6+ months were present in 3 patients who previously demonstrated disease progression within 6 months of autologous stem cell transplantation. Levels of CAR T cells peaked within 2 weeks and remained detectable 1 to 6+ months after infusion. Updated results will be presented.
Conclusion
Additional follow up of patients enrolled in the ZUMA-1 trial demonstrated durable complete remissions after a single dose of KTE-C19, with no new KTE-C19-related adverse events. The KTE-C19 regimen and central, streamlined manufacturing process were safe and feasible for future studies. The phase 2 portion of the ZUMA-1 clinical trial (NCT02348216) is ongoing.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemorefractory, Immunotherapy, Lymphoma, T cell
Abstract: S791
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most prevalent hematologic malignancy in the US and the 5th most deadly cancer with nearly 19,790 deaths/year. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, representing 25-35% of new cases annually. Approximately 1 in 3 patients treated in the first line will be refractory to treatment or relapse post-treatment and represent a significant unmet medical need. Patients with relapsed/refractory B-cell malignancies demonstrated durable remissions when treated with CD28/CD3zeta anti-CD19 CAR T cells at the National Cancer Institute (NCI) (Kochenderfer, JCO 2015; NCT00924326). KTE-C19 includes the same CAR construct as that used in the NCI trial, but is centrally manufactured in a streamlined 6- to 8-day process. Updated data from the phase 1 portion of the ZUMA-1 clinical trial are reported.
Aims
The primary goal was to determine the safety of KTE-C19. Secondary aims included evaluation of overall response rate, duration of response, blood concentrations of CAR T cells, and serum cytokine levels.
Methods
Patients with relapsed/refractory aggressive B-cell NHL were treated with a single target dose of 2 × 106 anti-CD19 CAR T cells (KTE-C19)/kg following a fixed dose of cyclophosphamide/fludarabine conditioning chemotherapy. Key inclusion criteria were ECOG 0-1 and chemo-refractory disease, which was defined as progressive or stable disease as best response to last line of therapy or disease progression ≤ 12 months after autologous stem cell transplantation. All patients provided informed consent.
Results
Seven patients received KTE-C19 as of January 15, 2016. A previously reported dose-limiting toxicity of grade 4 cytokine release syndrome and neurotoxicity occurred in one patient. All other grade ≥ 2 cytokine release syndrome and neurotoxicity adverse events resolved within one month. There were no other adverse events due to KTE-C19 after one month post-dosing. The overall response rate was 71%, with a complete response rate of 57%. Ongoing complete responses of 3 to 6+ months were present in 3 patients who previously demonstrated disease progression within 6 months of autologous stem cell transplantation. Levels of CAR T cells peaked within 2 weeks and remained detectable 1 to 6+ months after infusion. Updated results will be presented.
Conclusion
Additional follow up of patients enrolled in the ZUMA-1 trial demonstrated durable complete remissions after a single dose of KTE-C19, with no new KTE-C19-related adverse events. The KTE-C19 regimen and central, streamlined manufacturing process were safe and feasible for future studies. The phase 2 portion of the ZUMA-1 clinical trial (NCT02348216) is ongoing.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemorefractory, Immunotherapy, Lymphoma, T cell
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 08:45 - 09:00
Location: Hall A1
Background
Non-Hodgkin lymphoma (NHL) is the most prevalent hematologic malignancy in the US and the 5th most deadly cancer with nearly 19,790 deaths/year. Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, representing 25-35% of new cases annually. Approximately 1 in 3 patients treated in the first line will be refractory to treatment or relapse post-treatment and represent a significant unmet medical need. Patients with relapsed/refractory B-cell malignancies demonstrated durable remissions when treated with CD28/CD3zeta anti-CD19 CAR T cells at the National Cancer Institute (NCI) (Kochenderfer, JCO 2015; NCT00924326). KTE-C19 includes the same CAR construct as that used in the NCI trial, but is centrally manufactured in a streamlined 6- to 8-day process. Updated data from the phase 1 portion of the ZUMA-1 clinical trial are reported.
Aims
The primary goal was to determine the safety of KTE-C19. Secondary aims included evaluation of overall response rate, duration of response, blood concentrations of CAR T cells, and serum cytokine levels.
Methods
Patients with relapsed/refractory aggressive B-cell NHL were treated with a single target dose of 2 × 106 anti-CD19 CAR T cells (KTE-C19)/kg following a fixed dose of cyclophosphamide/fludarabine conditioning chemotherapy. Key inclusion criteria were ECOG 0-1 and chemo-refractory disease, which was defined as progressive or stable disease as best response to last line of therapy or disease progression ≤ 12 months after autologous stem cell transplantation. All patients provided informed consent.
Results
Seven patients received KTE-C19 as of January 15, 2016. A previously reported dose-limiting toxicity of grade 4 cytokine release syndrome and neurotoxicity occurred in one patient. All other grade ≥ 2 cytokine release syndrome and neurotoxicity adverse events resolved within one month. There were no other adverse events due to KTE-C19 after one month post-dosing. The overall response rate was 71%, with a complete response rate of 57%. Ongoing complete responses of 3 to 6+ months were present in 3 patients who previously demonstrated disease progression within 6 months of autologous stem cell transplantation. Levels of CAR T cells peaked within 2 weeks and remained detectable 1 to 6+ months after infusion. Updated results will be presented.
Conclusion
Additional follow up of patients enrolled in the ZUMA-1 trial demonstrated durable complete remissions after a single dose of KTE-C19, with no new KTE-C19-related adverse events. The KTE-C19 regimen and central, streamlined manufacturing process were safe and feasible for future studies. The phase 2 portion of the ZUMA-1 clinical trial (NCT02348216) is ongoing.
Session topic: Aggressive lymphoma with emphasis on novel agents
Keyword(s): Chemorefractory, Immunotherapy, Lymphoma, T cell
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