A Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3)

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.

MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported. 95% CI was calculated by Clopper-Pearson method.

CR: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. Percentage of participants with CR was reported. 95% CI was calculated by Clopper-Pearson method.

CRi: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. Percentage of participants with CRi was reported. 95% CI was calculated by Clopper-Pearson method.

DOR was defined as the time from first CR or CRi to relapse or any death in the absence of documented relapse. CR and CRi are defined in Outcome Measures 4 and 5. Relapse: ≤ 5% blasts by morphology in BM; or circulating leukemia present in PB; or CNS EMD of CNS-2 (detectable CSF blast cells in a sample of CSF with < 5 white blood cells [WBCs] per mm^3 with neurological changes) or CNS-3 (detectable CSF blast cells in a sample of CSF with ≥ 5 WBCs per mm^3 with or without neurological changes); or progressive disease (PD): at least one of the following (≥ 50% increase from nadir in the sum of the products of at least two lymph nodes, or if a single node is involved at least a 50% increase in the product of the diameters of this one node; at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis; ≥ 50% increase in size of splenic, hepatic or any other non-nodal lesion). Kaplan-Meier (KM) estimates was used for analyses.

OCR rate: percentage of participants achieving CR+CRi. CR: ≤ 5% blasts by morphology in BM; ANC ≥1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to ≤l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) 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% CI was calculated by Clopper-Pearson method.

Percentage of participants with MRD negative remission among CR participants was reported. MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. CR: ≤5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to ≤ l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. 95% CI was calculated by Clopper-Pearson method.

Percentage of participants with MRD negative remission among CRi participants was reported. MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. CRi: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to ≤l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions. 95% CI was calculated by Clopper-Pearson method.

OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Participants who had not died by the analysis data cutoff date were censored at their last contact date. KM estimates was used for analyses.

RFS: time from brexucabtagene autoleucel infusion to date of disease relapse or death from any cause. Participants not meeting criteria for relapse by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who had not achieved a CR or CRi at analysis data cutoff were evaluated as an RFS event at Day 0. CR and CRi are defined in Outcome Measures 4 and 5. Relapse is defined in Outcome Measure 6. KM estimates was used for analyses.

An AE was any untoward medical occurrence in a participant after brexucabtagene autoleucel infusion, which did not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs included all AEs with onset on or after initiation of the brexucabtagene autoleucel infusion.

Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening.

Grading categories are determined by CTCAE version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening.

The EQ-5D-5 levels(EQ-5D-5L)is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal.It is a self-reported questionnaire used to assess the overall health status of participant scoring 5 dimensions of health: mobility,self-care,usual activities,pain/discomfort and anxiety/depression.Each dimension has 5 levels:no problems,slight problems,moderate problems,severe problems,and extreme problems.EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by a formula that attaches values (called QOL utilities)to each of the levels in each dimension.EQ-5D Summary Index values range from -0.11(worst health) to 1.00(perfect health).This decision results in a 1-digit number that shows the level for that dimension. The digits for 5 dimensions can be combined to 5-digit number that show the participant's health.Higher scores of EQ-5D-5L indicate better health.

EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The EQ-5D-VAS records the participant's self-rated health on a 20-cm vertical visual analogue scale and is asked to make a global assessment of their current state of health with 0 indicating the worst health they can imagine and 100 indicating the best health they can imagine. Higher scores indicated a better health state.