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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
An autologous, dual-targeting CD19/20 CAR T-cell candidate.
An autologous CD19 CAR T-cell therapy
An autologous CD19 CAR T-cell therapy
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
NOT_YET_RECRUITINGHonor Health
Scottsdale, Arizona, United States
RECRUITINGMayo Clinic Arizona
Scottsdale, Arizona, United States
RECRUITINGUniversity of Arkansas
Little Rock, Arkansas, United States
Event free survival
The time interval from treatment initiation until the occurrence of a specific event of interest.
Time frame: 36 months
Overall Response Rate
Best Overall Response per Lugano Criteria
Time frame: 36 months
Complete Response Rate
Complete Response per Lugano Criteria
Time frame: 36 months
Progression Free Survial
The length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Time frame: 36 months
Overall Survival
The length of time from either the date of diagnosis or the start of treatment for a disease, that patients diagnosed with the disease, are still alive.
Time frame: 6 years
Incidence and severity adverse events
To assess safety defined as type and frequency of AEs, serious adverse events (SAEs), and laboratory abnormalities.
Time frame: 36 months
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Cedars-Sinai Medical Center
Los Angeles, California, United States
RECRUITINGUniversity of California, Los Angeles (UCLA)
Los Angeles, California, United States
NOT_YET_RECRUITINGUniversity of California, Irvine
Orange, California, United States
NOT_YET_RECRUITINGUniversity of Colorado
Aurora, Colorado, United States
RECRUITINGColorado Blood Cancer Institute
Denver, Colorado, United States
RECRUITINGMedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
NOT_YET_RECRUITING...and 28 more locations