A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy
Purpose
This Phase 3 study compares rondecabtagene autoleucel (ronde-cel), a dual-targeting CD19/CD20 CAR T-cell therapy, with investigator's choice of CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphoma in the second-line setting.
Conditions
- Large B-cell Lymphoma
- Lymphoma, B-Cell
- Relapsed Non-Hodgkin Lymphoma
- Refractory Non-Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- Non-Hodgkin Lymphoma Refractory/ Relapsed
- Diffuse Large B Cell Lymphoma (DLBCL)
- Diffuse Large B Cell Lymphoma Refractory
- Diffuse Large B Cell Lymphoma Relapsed
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- CAR T cell naïve and eligible to receive a CD19 CART-cell therapy 2. Histologically confirmed large B-cell lymphoma, including the following types defined by (WHO 2022) or International Consensus Classification (2022) - Diffuse large B-cell lymphoma (DLBCL) - Transformations of indolent B-cell lymphomas (excluding Richter's transformation) - DLBCL/High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 rearrangements - High-grade B-cell lymphoma (HGBCL) not otherwise specified (HGBCL NOS) - Primary mediastinal large B-cell lymphoma (PMBCL) - Grade 3B follicular lymphoma/large cell follicular lymphoma (FL3B) 3. Relapsed or refractory disease after anti-CD20 antibody and anthracycline-containing first-line chemoimmunotherapy 4. Measurable disease by presence of [18F]-fluorodeoxyglucose PET/CT positive lesion during Screening per Lugano Criteria 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 6. Adequate hematological, renal, hepatic, pulmonary, and cardiac function
Exclusion Criteria
- Patients ineligible to receive CD19 CAR T-cell therapy 2. Primary CNS lymphoma 3. Patients with primary cutaneous LBCL, human herpes virus-8 positive lymphoma, Burkitt lymphoma, T cell histiocyte-rich lymphoma, or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter's transformation) 4. Patients with prior history of malignancy, other than aggressive relapsed or refractory LBCL, unless the patient has been free of the disease for ≥ 2 years 5. Patients with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment 6. Active autoimmune disease requiring ongoing systemic immunosuppressive therapy. Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Rondecabtagene autoleucel |
|
|
|
Active Comparator Investigator's Choice CD19 |
axicabtagene ciloleucel, lisocabtagene maraleucel |
|
Recruiting Locations
Westwood, Kansas 66205
More Details
- Status
- Recruiting
- Sponsor
- Lyell Immunopharma, Inc.
Detailed Description
PiNACLE-H2H is a Phase 3 randomized controlled trial comparing the efficacy and safety of rondecabtagene autoleucel (ronde-cel, formerly known as LYL314) against the currently approved cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T-cell therapies (axicabtagene ciloleucel [axi-cel] or lisocabtagene maraleucel [liso-cel]), in patients with aggressive LBCL that has relapsed or is refractory to first-line anti-CD20 antibody and anthracycline-containing chemotherapy. Patients will be randomized (1:1) before leukapheresis to receive either: - Ronde-cel; or - Investigator's choice of axi-cel or liso-cel Most patients who receive currently approved CD19-directed CAR T-cell therapies, including axi-cel and liso-cel, still experience progressive disease, often due to mechanisms such as CD19 antigen loss or T-cell exhaustion. Ronde-cel is a novel, autologous, dual-targeting CD19/CD20 CAR T-cell product candidate enriched for CD62L-positive naïve and central memory T cells, which are associated with enhanced proliferation capacity and persistence. Ronde-cel is an "OR"-gated CAR construct that can fully activate upon recognition of either CD19 or CD20, aiming to improve durability of response despite antigen heterogeneity. Approximately 400 participants will be enrolled. CAR T-cell therapy in both arms will be administered as a single intravenous infusion following fludarabine and cyclophosphamide lymphodepletion. Participants will be followed for 3 years for safety and efficacy, with long-term follow-up extending to 15 years.