A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of Rondecabtagene Autoleucel, a CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy in Participants With Aggressive B-Cell Non-Hodgkin Lymphoma

Summary

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of rondecabtagene autoleucel (ronde-cel) also known as LYL314, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.

Detailed description

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of ronde-cel, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma. Five cohorts of participants will be enrolled: Cohort 1: (3rd or later line, 3L+) Participants who have received least two prior lines of treatment Cohort 2: (CAR T-cell experienced, 3L+): Participants who have received at least two prior lines of treatment including one prior CAR T. Cohort 3: (second line, 2L) Participants with refractory disease or relapse within one year of first-line therapy (second-line). Cohort 4: (TCE-experienced, 3L+) Participants have received prior T-cell engager therapy and have received at least two prior lines of treatment including one TCE therapy and have not received prior CAR T. Cohort 5: (high-risk 1st line) Participants receiving first-line treatment who remain with disease on positron emission tomography scanning (PET-positive) after 2 to 3 cycles of standard-of-care chemoimmunotherapy and have not received prior CAR T. Up to approximately 150 participants (across all cohorts) will be enrolled in the dose finding Phase 1 part of the study. The Phase 2 pivotal study (PiNACLE) will expand enrollment of Cohort 1 to approximately 120 participants to further evaluate the safety and efficacy of ronde-cel. Ronde-cel treatment consists of a single administration of CAR transduced autologous T-cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered over 3 days. Individual participants will remain in the active post-treatment follow-up (PTFU) period for approximately 2 years. Participants will continue in long-term follow-up (LTFU) for 15 years from ronde-cel treatment.

Arms & interventions

• DrugRondecabtagene autoleucel (ronde-cel)

  CAR T-cell therapy

• DrugFludarabine

  Conditioning chemotherapy

• DrugCyclophosphamide

  Conditioning chemotherapy

Outcome measures

Eligibility criteria