Table 3.

Overview of the most relevant clinical trials for treatment approval.

Trade Name Generic Name	Most Relevant Clinical Trials	Summary of Most Relevant Results
KYMRIAH® Tisagenlecleucel	NCT02435849—Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients (ELIANA) [44] NCT02445248—Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients (JULIET) [45] NCT02228096—Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients (ENSIGN) [46] NCT03568461—Efficacy and Safety of Tisagenlecleucel in Adult Patients With r/r Follicular Lymphoma (ELARA) [47] NCT01029366—CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy [48] NCT01747486—Dose Optimization Trial of CD19 Redirected Autologous T Cells [49] NCT02030847—Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia [50] NCT02030834—Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas [51]	ELIANA: primary end point: ORR 82.3% (95% CI, 72.1 to 90.0); secondary end points: BOR 82.1% (95% CI, 70.8 to 90.4); BOR with MRD negative BM 81.0% (95% CI, 70.6 to 89.0); total SAEs 79.75%, CRS 63.29%, ICANS: 3.75% [44] JULIET: primary end point: ORR 52% (95% CI, 41 to 62); secondary end points: 12-month median RFS 65%; CRS ≥ 3: 22%, ICANS ≥ 3: 12% [52] ENSIGN: primary end point ORR: 70.3% (95% CI, 57.6 to 81.1); secondary end points: median EFS 15.6 months (95% CI, 6.4 to NA), median OS 29.9 months (95% CI, 15.1 to 42.4); total SAEs 81.25%, CRS 64.06%, ICANS 6.25% [46] ELARA: primary end point CRR: 69.1% (95% CI, 58.8 to 78.3); secondary end points: ORR 86.2 (95% CI, 77.5 to 92.4), total SAEs 43.3%, CRS 19.59%, ICANS 1.03% [47]
YESCARTA® Axicabtagene ciloleucel	NCT02348216—Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1) [53] NCT03105336—A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With r/r Indolent Non-Hodgkin Lymphoma (ZUMA-5) [54] NCT03153462—Axicabtagene Ciloleucel Expanded Access Study (ZUMA-9) [55] NCT03761056—Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma (ZUMA-12) [56] NCT03391466—Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With r/r Diffuse Large B Cell Lymphoma (ZUMA-7) [57]	ZUMA-1: primary end points: cohort 1 ORR 82% (95% CI, 71 to 90), cohort 2 ORR 83% (95% CI, 63 to 95), cohort 3: CRS ≥ 3: 3%, ICANS ≥ 3: 39%, ICANS 5: 3%, cohort 4: CRS ≥ 3: 2%, ICANS ≥ 3: 17%, cohort 5: CRS ≥ 3: 2%, ICANS ≥ 3: 12%, cohort 6: CRS ≥ 3: 0%, ICANS ≥ 3: 15%; total SAEs 71.43% [53] ZUMA-5: primary end point: ORR 94% (95% CI, 88–97) in FL and 77% (95% CI, 59–90) in MZL; key secondary end points: median PFS 40.2 months in FL, not reached in MZL; FL: total SAEs 11%, CRS ≥ 3: 0%, ICANS ≥ 3: 0%; MZL: total SAEs 14%, CRS ≥ 3: 11%, ICANS ≥ 3: 4% [81] ZUMA-12: primary end point: CRR 78% (95% CI, 62 to 90); secondary end points: ORR 89% (95% CI, 75 to 97), median OS 24.5 months (95% CI, 3.6 to 24.5), total SAEs 45% [56] ZUMA-7: primary end point: 25-month follow-up: EFS 8.3 vs. 2.0 months, HR 0.4, (95% CI, 0.31 to 0.51, p < 0.001); secondary end points: ORR 83% vs. 50% (p < 0.001), CR 65% vs. 32%, total SAEs 91% vs. 83%; CRS ≥ 3: 6% vs. 0%, neurologic events ≥ 3: 21% vs. 1% [82]
TECARTUS® Brexucabtagene autoleucel	NCT02601313—Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With r/r Mantle Cell Lymphoma (Cohort 1 and Cohort 2) (ZUMA-2) [83] NCT02614066—A Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With r/r B-precursor Acute Lymphoblastic Leukemia (ZUMA-3) [84] NCT02625480—Study Evaluating Brexucabtagene Autoleucel (KTE-X19) in Pediatric and Adolescent Participants With r/r B-precursor Acute Lymphoblastic Leukemia or r/r B-Cell Non-Hodgkin Lymphoma (ZUMA-4) [85] NCT03624036—Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With r/r Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ZUMA-8) [86] NCT04162756—Study of Brexucabtagene Autoleucel (KTE-X19) for the Treatment of Individuals With r/r MCL (ZUMA-18) [87]	ZUMA-2: primary end points: ORR 93% (95% CI, 84 to 98); secondary end points: CRR 67% (95% CI, 53 to 78), 12-month PFS 61% and OS 83%; CRS ≥ 3: 15%, ICANS ≥ 3: 31% [88] ZUMA-3: primary end points: CRR 70.9% (95% CI, 57 to 82); secondary end points: MRD negativity 76% (95% CI, 63 to 87), median DOR 12.8 months (95% CI, 8.7 to NA), median OS 18.2 (95% CI, 15.9 to NA), total SAEs: dose-dependent from 100% to 75%; CRS ≥ 3: 24%, ICANS ≥ 3: 25% [84,89,90] ZUMA-8: primary end point: dose limiting toxicities (DLTs): first-stage cohort 1: 0%, first-stage cohort 2: 0%, second-stage cohort 3: 33.3%, second-stage cohort 4A: 0%; secondary end points: ORR: first-stage cohort 1: 50% (95% CI, 11.8 to 88.2), first-stage cohort 2: 33% (95% CI, 0.8 to 90.6), second-stage cohort 3: 100% (95% CI, 29.2 to 100), second-stage cohort 4a: 0% (0.0 to 70.8) [86] ZUMA-18: ORR: 87%; median OS not yet reached at 33.5 months of follow-up; no new safety signals were detected
ABECMA® Idecabtagene vicleucel	NCT03361748—Efficacy and Safety Study of bb2121 in Subjects With r/r Multiple Myeloma (KarMMa) [91] NCT03601078—An Efficacy and Safety Study of bb2121 in Subjects With r/r Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma (KarMMa-2) [92] NCT03651128—Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With r/r Multiple Myeloma (RRMM) (KarMMa-3) [93] NCT02658929—Study of bb2121 in Multiple Myeloma [94] NCT02786511—Longterm Follow-up of Subjects Treated With bb2121 [95]	KarMMa: primary end point: ORR 73% (95% CO, 66 to 81; p < 0.001); secondary end points: CRR 33%, VGPR or better 52%, MRD negativity 26% (95% CI, 19 to 34), median DOR 10.7 months (95% CI, 9.0 to 11.3), median PFS 8.8 months (95% CI, 5.6 to 11.6), total SAEs 99%, CRS ≥ 3: 5%, ICANS ≥ 3: 3% [96] KarMMa-3: primary end point: at 18.6 months mPFS 13.3 vs. 4.4 months (HR 0,49, 95% CI, 0.38 to 0.65; p < 0.001); secondary end points: ORR 71% vs. 42% (p < 0.001), CR 39% vs. 5%; total SAE 93% vs. 75%, CRS ≥ 3: 5%, ICANS ≥ 3: 3% [97]
BREYANZI® Lisocabtagene maraleucel	NCT02631044—Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001) [98] NCT03484702—Trial to Determine the Efficacy and Safety of JCAR017 in Adult Participants With Aggressive B-Cell Non-Hodgkin Lymphoma (TRANSCENDWORLD) [99] NCT03744676—A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for r/r B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007) [100] NCT03310619—A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With r/r B-cell Malignancies (PLATFORM) [101] NCT03483103—Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006) [102] NCT03331198—Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) [103] NCT03743246—A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With r/r B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL) [104] NCT03575351—A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM) [105]	TRANSCEND-NHL-001: primary end point: ORR 73% (95% CI, 66.8 to 78.0); secondary end points: CRR 53% (95% CI, 46.8 to 59.4); 12-month DOR 54.7% (95% CI, 46.7 to 62.0), median PFS 6.8 months (95% CI, 3.3 to 14.1), 12-month OS 57.9% (95% CI, 51.3 to 63.8); total SAE 79%, CRS ≥ 3: 2%, ICANS ≥ 3: 10% [106,107] TRANSCEND-OUTREACH-007: primary end points: CRS ≥3: 0.0% (95% CI, 0.0 to 4.4), ICANS ≥3: 9.8% (95% CI, 4.3 to 18.3); secondary end points: total SAE: 74.4%, ORR 80.5% (95% CI, 70.3 to 88.4), CRR 53.7 (95% CI, 42.3 to 64.7), median DOR 14.75 months (95% CI, 5.03 to NA), median DOCR NA (95% CI, 16.59 to NA), median PFS 5.83 months (95% CI, 0.7 to 24.5), median OS 22.01 months (95% CI, 1.0 to 27.3) [100] TRANSCEND-PILOT-017006: primary end point: ORR 80.3% (95% CI, 68.2 to 89.4); secondary end points: total SAE 78.7%, CRR 54.1% (95% CI, 40.8 to 66.9), median DOR 23.26 months (95% CI, 6.24 to NA), median PFS 9.03 (95% CI, 4.17 to NA), median EFS 7.23 months (95% CI, 3.22 to 24.28), median OS NA (95% CI, 16.33 to NA), CRS ≥ 3: 2%, ICANS ≥ 3: 5% [102,108] TRANSFORM: primary end point: median EFS NA (95% CI, 9.5 to NA) vs. 2.4 months (95% CI, 2.2 to 4.9), HR 0.356 (0.243 to 0.522); secondary end points: CRR 68% (95% CI, 63.7 to 82.5) vs. 40% (95% CI, 33.2 to 54.2) p < 0.0001, median PFS NA (95% CI, 12.6 to NA) vs. 6.2 months (95% CI, 4.3 to 8.6), HR 0.400 (95% CI, 0.261–0.615) p < 0.0001, median OS NA (95% CI, 29.5 to NA) vs. 29.9 (95% CI, 17.9 to NA), HR 0.724 (95% CI, 0.443 to 1.183) p = 0.099, total SAE 85% vs. 81%, CRS ≥3: 1%, ICANS ≥ 3: 4% [105,109]
CARVYKTI® Ciltacabtagene autoleucel	NCT03548207—A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) [110] NCT04133636—A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2) [111] NCT04181827—A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4) [112]	CARTITUDE-1: primary end point: ORR 97.9% (95% CI, 92.7 to 99.7); secondary end points: sCR 82.5% (95% CI, 73.4 to 89.4), MRD negative sCR 44.3% (95% CI, 34.2 to 54.8), 27-month OS 70.4%, total SAE 91%, CRS ≥ 3: 5.1% (one related death), ICANS ≥ 3: 12.3% (one related death) [113,114] CARTITUDE-2: primary end point: MRD negativity 35% (95% CI, 15.4 to 59.2); secondary end points: ORR 60.0% (95% CI, 36.1 to 80.9), median DOR 11.5 months (95% CI, 7.0 to NA), total SAE 95%, CRS ≥ 3: 0%, ICANS ≥ 3: 10% [115] CARTITUDE-4: primary end point: 12-month PFS 75.9% (95% CI, 69.4 to 81.1) vs 48.6% (95% CI, 41.5 to 55.3); secondary end points: ORR 84.6% vs. 67.3%, HR 2.2 (95% CI, 1.5 to 3.1) p < 0.001, CR or better 73.1% vs. 21.8%, HR 2.9 (95% CI, 2.3 to 3.7) p < 0.001; total SAE 96.6% vs. 94.2%, CRS ≥ 3: 1.1%, ICANS ≥ 3: 2.8% [115]