Phase 3
Completed N=184
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
Lymphoma, Non-Hodgkin
Source: ClinicalTrials.gov NCT03575351 ↗
Enrolled (actual)
184
Serious AEs
45.4%
Results posted
Aug 2025
Primary outcomePrimary: Event-free Survival (EFS) Per Independent Review Committee (IRC) — 2.4; 29.5 Months
◆ Published Evidence
Highly cited
371citations · ~124 / year
Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study.
Summary
The study will be conducted in compliance with the International Council for Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements.
This is a randomized, open-label, parallel-group, multi-center trial in adult subjects with Relapsed or refractory (R/R) aggressive Non-Hodgkin lymphoma (NHL) to compare safety and efficacy between the standard of care (SOC) strategy versus JCAR017 (also known as lisocabtagene maraleucel or liso-cel). Subjects will be randomized to either receive SOC (Arm A) or to receive JCAR017 (Arm B).
All subjects randomized to Arm A will receive Standard of care (SOC) salvage therapy (R-DHAP, RICE or R-GDP) as per physician's choice before proceeding to High dose chemotherapy (HDCT) and Hematopoietic stem cell transplant (HSCT).
Subjects from Arm A may be allowed to cross over and receive JCAR017 upon confirmation of an EFS event.
Subjects randomized to Arm B will receive Lymphodepleting (LD) chemotherapy followed by JCAR017 infusion.
Linked Publications (5)
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Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study.
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Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study.
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Plain language summary of the TRANSFORM study primary analysis results: liso-cell as a second treatment regimen for large B-cell lymphoma following failure of the first treatment regimen.
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Estimating the Cost per Clinical Outcome of Second-Line Liso-Cel Versus Autologous Stem Cell Transplantation in Patients with Transplantation-Intended Relapsed/Refractory Large B Cell Lymphoma.
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Circulating Tumor DNA Assessment of Disease Response in Large B-Cell Lymphoma: Lisocabtagene Maraleucel Versus Autologous Stem Cell Transplantation Standard Therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Event-free Survival (EFS) Per Independent Review Committee (IRC) |
2.4; 29.5 | — |
| SECONDARY Complete Response Rate (CRR) |
43.5; 73.9 | — |
| SECONDARY Number of Participants With Complete Response (CR) |
40; 68 | — |
| SECONDARY Progression-free Survival (PFS) |
6.2; NA | — |
| SECONDARY Overall Survival (OS) |
NA; NA | — |
| SECONDARY Overall Response Rate (ORR) |
48.9; 87.0 | — |
| SECONDARY Duration of Response (DoR) Per Independent Review Committee (IRC) |
9.1; NA | — |
| SECONDARY Number of Participants With Progression-free Survival on Next Line of Treatment (PFS-2) |
15; 10; 60; 40; 8; 8 | — |
| SECONDARY Event-free Survival (EFS) Rate |
36.2; 68.1; 22.6; 57.0; 22.6; 52.6 | — |
| SECONDARY Progression-free Survival (PFS) Rate |
51.7; 73.7; 31.3; 63.0; 31.3; 58.2 | — |
| SECONDARY Overall Survival (OS) Rate |
88.9; 93.4; 72.0; 83.5; 61.7; 73.3 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
90; 92; 57; 60; 1; 20 | — |
| SECONDARY Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs) |
45; 43; 29; 23; 0; 9 | — |
| SECONDARY Change From Baseline in Hematology Parameters 1: Hemoglobin |
-16.98; -14.94; -25.00; -30.83; -15.78; -22.00 | — |
| SECONDARY Change From Baseline in Selected Hematology Parameters 2 |
0.815; -3.219; -0.870; -3.445; -2.234; -1.180 | — |
| SECONDARY Change From Baseline in Selected Chemistry Parameters 1 |
17.22; -0.52; 4.00; -3.40; 2.53; -3.00 | — |
| SECONDARY Change From Baseline in Selected Chemistry Parameters 2 |
-0.023; 0.009; -0.080; -0.063; 0.007; -0.200 | — |
| SECONDARY Overall Response Rate (ORR) by Subgroups |
51.7; 86.7; 100; 42.9; 81.8; 33.3 | — |
| SECONDARY Event-free Survival (EFS) by Subgroups |
3.0; NA; NA; 2.2; 4.6; 2.2 | — |
| SECONDARY Progression-free Survival (PFS) by Subgroups |
6.0; NA; NA; 4.3; 5.8; NA | — |
| SECONDARY Overall Survival (OS) by Subgroups |
NA; NA; NA; 16.3; 13.3; NA | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) |
-9.55; -5.23; -2.78; 12.36; 5.30; 12.50 | — |
| SECONDARY Change From Baseline in the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-Lym) |
-0.76; 0.35; 2.19; 3.52; 0.11; 5.48 | — |
| SECONDARY Hospital Resource Utilization (HRU) Results |
74; 87; 42; 44; 2; 6 | — |
| SECONDARY Percentage of Participants Completing High Dose Chemotherapy (HDCT) |
47.3 | — |
| SECONDARY Percentage of Participants Completing Hematopoietic Stem Cell Transplant (HSCT) |
47.3 | — |
Eligibility Criteria
Inclusion Criteria
- Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]), primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large B-cell lymphoma (THRBCL) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology.
- Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
- [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
- Adequate organ function
- Participants must agree to use effective contraception
Exclusion Criteria
- Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
- Subjects planned to undergo allogeneic stem cell transplantation.
- Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL, Burkitt lymphoma or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter transformation).
- Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following noninvasive malignancies:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
- Other completely resected stage 1 solid tumor with low risk for recurrence
- Treatment with any prior gene therapy product.
- Subjects who have received previous CD19-targeted therapy.
- Subjects with active hepatitis B, or active hepatitis C are excluded. Subjects with negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy. Subjects with a history of or active human immunodeficiency virus (HIV) are excluded.
- Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
- Active autoimmune disease requiring immunosuppressive therapy.
- History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
- History or presence of clinically relevant central nervous system (CNS) pathology
- Pregnant or nursing (lactating) women.
Data sourced from ClinicalTrials.gov (NCT03575351) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.