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
NOT_YET_RECRUITINGMayo Clinic Arizona
Scottsdale, Arizona, United States
NOT_YET_RECRUITINGUniversity of Arkansas
Little Rock, Arkansas, United States
NOT_YET_RECRUITINGEvent 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
NOT_YET_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
NOT_YET_RECRUITINGColorado Blood Cancer Institute
Denver, Colorado, United States
RECRUITINGMedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
NOT_YET_RECRUITING...and 30 more locations