NCT07188558

A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy

A Phase 3 Randomized Controlled Trial of Rondecabtagene Autoleucel , an Autologous, Dual-targeting CD19/CD20 CAR T-Cell Product Candidate, Vs. Investigator's Choice of CD19 CAR T-Cell Therapy in Patients With Relapsed or Refractory Large B-Cell Lymphoma in the Second-line Setting

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Sponsor: Lyell Immunopharma, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

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

Interventions

Type	Name	Description
BIOLOGICAL	rondecabtagene autoleucel	An autologous, dual-targeting CD19/20 CAR T-cell candidate.
BIOLOGICAL	axicabtagene ciloleucel	An autologous CD19 CAR T-cell therapy
BIOLOGICAL	lisocabtagene maraleucel	An autologous CD19 CAR T-cell therapy

Timeline

• Start date: 2026-01-12
• Primary completion: 2029-12-01
• Completion: 2032-01-01
• First posted: 2025-09-23
• Last updated: 2026-03-04

Locations

39 sites across 1 country: United States

Regulatory

• FDA-regulated drug study