Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
270 participants
INTERVENTIONAL
2023-05-09
2031-06-30
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase 1 CAR T naïve (Cohort 1)
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Phase 1 CAR T experienced (Cohort 2)
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Phase 1 Refractory disease or relapse within one year of first-line therapy (Cohort 3)
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Phase 1 Received T-cell engager (TCE) therapy (Cohort 4)
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Phase 1 Receiving first-line treatment for high-risk large B-cell lymphoma (Cohort 5)
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Phase 2 CAR T naïve (Cohort 1)
Single dose determined during Phase 1.
LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Interventions
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LYL314
CAR T-cell therapy
Fludarabine
Conditioning chemotherapy
Cyclophosphamide
Conditioning chemotherapy
Eligibility Criteria
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Inclusion Criteria
2. Willing and able to provide written informed consent
3. 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)
4. 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
5. 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).
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
8. Absolute neutrophil count (ANC) ≥ 1000/uL
9. Platelet count ≥ 50,000/uL
10. Absolute lymphocyte count (ALC) ≥ 200/uL
Other protocol-defined criteria apply.
Exclusion Criteria
2. Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or by lumbar puncture. Participants with prior evidence of brain metastasis treated at least 8 weeks prior to enrollment will not be excluded for participation if CNS disease is deemed stable at the time of study enrollment
3. History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
4. Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome, known vascular invasion)
5. Received the following therapies in the specified time frame prior to enrollment/leukapheresis
1. Any systemic therapy within 2 weeks
2. Any systemic inhibitory/stimulatory immune checkpoint molecule therapy within 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists)
3. Fludarabine within 12 weeks
4. Alemtuzumab, bendamustine or antithymocyte globuline (ATG) within 6 months
5. Any T cell engager/bispecific antibody therapy such as CD20/CD3 or CD19/CD3 bispecific antibodies within 4 weeks
6. Any experimental therapy within 4 weeks or 5 half-lives (whichever is shorter)
6. Received radiation therapy within 3 weeks prior to enrollment/leukapheresis
7. Experiencing non-hematologic toxicities due to prior therapy. Exceptions include: stable and recovered to grade ≤ 1 or non-clinically significant toxicities such as (1) alopecia, (2) toxicities where Grade 2 is solely defined by participant receiving hormone replacement therapy for endocrinopathies resulting from previous checkpoint inhibitor therapy, (3) Grade 2 lymphopenia, and (4) hearing loss or Grade 2 neuropathy associated with prior treatment with taxanes or platinating agents
8. History of allogeneic stem cell or solid organ transplantation
9. Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment/leukapheresis
10. History of prior genetically modified cell therapy other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). For all other CAR T cell therapy treatments, discussion with the Sponsor's Medical Monitor is required
11. Primary immunodeficiency
12. History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. Participants who have other autoimmune condition(s) considered to be associated with underlying malignancy may be enrolled in the study after discussion with and approval of the Medical Monitor.
Other protocol-defined criteria apply.
18 Years
ALL
No
Sponsors
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Lyell Immunopharma, Inc.
INDUSTRY
Responsible Party
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Locations
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University of California-Irvine Medical Center
Irvine, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
University of California, Los Angeles (UCLA) Medical Center
Los Angeles, California, United States
Scripps Clinic
San Diego, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Augusta University Medical Center
Augusta, Georgia, United States
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
University of Louisville Brown Cancer Center
Louisville, Kentucky, United States
Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States
Corewell Health
Grand Rapids, Michigan, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, United States
Montefiore Medical Center
The Bronx, New York, United States
University of Cincinnati (UC) Physicians Company, LLC
Cincinnati, Ohio, United States
Lehigh Valley Topper Cancer Center Institute
Allentown, Pennsylvania, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Baylor University Medical Center
Dallas, Texas, United States
Texas Transplant Institute
San Antonio, Texas, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Intermountain Healthcare
Salt Lake City, Utah, United States
Virginia Oncology Associates
Norfolk, Virginia, United States
Virginia Commonwealth University-Massey Cancer Center
Richmond, Virginia, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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Central Contacts
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Other Identifiers
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LYL314-101
Identifier Type: -
Identifier Source: org_study_id