Study of LYL314 in Aggressive Large B-Cell Lymphoma
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
LYL314-101 (primary)
NCI-2023-03746
MPCT-012L
Summary
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.
Objectives
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.
Eligibility
- Age 18 years or older at time of informed consent
- Willing and able to provide written informed consent
- Histologically confirmed aggressive NHL, including the following types defined by the World Health Organization (WHO 2017):
- DLBCL
- DLBCL arising from follicular lymphoma (transformed FL, tFL)
- Primary mediastinal (thymic) large B-cell lymphoma (PMBCL)
- High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement (HGBL)
- Grade 3B follicular lymphoma/Large cell follicular lymphoma (FL3B)
- Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3. Prior therapy must have included:
- Anti-CD20 monoclonal antibody, and
- An anthracycline containing chemotherapy regimen
- Participants with tFL must have received at least one of their prior lines of therapy after transformation to DLBCL 4b. Cohort 5 (High-risk first-line) participants must have high-risk large B-cell lymphoma
- Relapsed or refractory disease, defined by the following:
- Disease progression after last regimen (including salvage therapy after autologous stem cell transplantation [ASCT]). In participants who have only received front-line therapy, progression should be = 12 months of first-line therapy (applicable for Cohort 3)
- In patients who received one line of therapy, refractory disease is defined as failure to achieve at least a PR after at least 4 cycles of therapy (applicable for Cohort 3)
- In patients who received two or more lines of therapy (Cohorts 1, 2, and 4), refractory disease is defined as failure to achieve a CR to last line of therapy (including CAR T and/or salvage therapy).
- At least 1 measurable lesion (per Lugano classification). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
- Absolute neutrophil count (ANC) = 1000/uL
- Platelet count = 50,000/uL
- Absolute lymphocyte count (ALC) = 200/uL Other protocol-defined criteria apply.
Treatment Sites in Georgia
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