Northside Hospital Cancer Institute Immunotherapy Program in collaboration with Lyell Immunopharma, Inc. is opening PINACLE-H2H a phase 3 randomized controlled trial to compare rondecabtagene autoleucel (ronde-cel; LYL314), a dual-targeting CD19/CD20 CAR T- cell product candidate, versus investigator's choice of CD19 CAR T- cell therapy in patients with relapsed or refractory large B-cell lymphoma in the second-line setting.

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.

If you have any questions, would like to discuss study logistics, or the eligibility of any patients, please contact Caitlin Guzowski, NH BMT/Leukemia Clinical Research Manager, at 404-851-8523 or caitlin.guzowski@northside.com

Study Design

Patients will be randomized (1:1) before leukapheresis to receive either:

• Ronde-cel; or
• Investigator's choice of axicabtagene autoleucel (axi-cel) or lisocabtagene maraleuceel (liso-cel)

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

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
• Active autoimmune disease requiring ongoing systemic immunosuppressive therapy