A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy
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.
Inclusion Criteria
- CAR T cell naïve and eligible to receive a CD19 CART-cell therapy
- 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)
- Relapsed or refractory disease after anti-CD20 antibody and anthracycline-containing first-line chemoimmunotherapy
- Measurable disease by presence of [18F]-fluorodeoxyglucose PET/CT positive lesion during Screening per Lugano Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hematological, renal, hepatic, pulmonary, and cardiac function Key
Exclusion Criteria
- Patients ineligible to receive CD19 CAR T-cell therapy
- Primary CNS lymphoma
- 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)
- 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
- Patients with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
- Active autoimmune disease requiring ongoing systemic immunosuppressive therapy. Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07188558.
Locations matching your search criteria
United States
Colorado
Aurora
Florida
Tampa
Ohio
Cleveland
Texas
Houston
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.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationLyell Immunopharma, Inc.
- Primary IDLYL314-102
- Secondary IDsNCI-2026-00303
- ClinicalTrials.gov IDNCT07188558