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

Summary

Objectives

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.