Study of LYL314 in Aggressive Large B-Cell Lymphoma

Description

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of LYL314, 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: Participants who have not received a prior CAR T-cell product (CAR T naïve) and have received at least two or more prior lines of treatment (third-line or later).

Cohort 2: Participants who have received a prior CAR T-cell product (CAR T experienced) and have received at least two or more prior lines of treatment including one CAR T-cell therapy.

Cohort 3: Participants with refractory disease or relapse within one year of first-line therapy (second-line).

Cohort 4: Participants who have received prior T-cell engager (TCE) therapy and have received at least two or more prior lines of treatment including one TCE therapy.

Cohort 5: Participants receiving first-line treatment for high-risk large B-cell lymphoma who remain with disease on positron emission tomography scanning (PET-positive) after 2 to 3 cycles of standard-of-care chemoimmunotherapy (high-risk first-line).

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 LYL314.

LYL314 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 LYL314 treatment.