Brief 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.
Brief Title
Study of Rondecabtagene Autoleucel in 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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
000-000-0000
Central Contact Email
clinicaltrials@lyell.com
Completion Date
Completion Date Type
Estimated
Conditions
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Large B-cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
1. Age 18 years or older
2. Willing and able to provide written informed consent
3. Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
4. Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
5. Relapsed or refractory disease.
6. At least 1 measurable lesion (per Lugano classification)
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/µL
9. Platelet count ≥ 50,000/µL
10. Absolute lymphocyte count (ALC) ≥ 200/µL
Other protocol-defined criteria apply.
Exclusion Criteria:
1. History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
2. Active central nervous system involvement
3. History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
4. Ongoing or impending oncologic emergency
5. Recent systemic anti-cancer therapy or radiation
6. Ongoing non-hematologic toxicities due to prior therapy
7. History of allogeneic stem cell or solid organ transplantation
8. Autologous stem cell transplantation within 6 weeks
9. History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no 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) (Cohort 2).
10. Primary immunodeficiency
11. History of autoimmune disease resulting in end organ injury or requiring recent therapy
Other protocol-defined criteria apply.
1. Age 18 years or older
2. Willing and able to provide written informed consent
3. Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
4. Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
5. Relapsed or refractory disease.
6. At least 1 measurable lesion (per Lugano classification)
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/µL
9. Platelet count ≥ 50,000/µL
10. Absolute lymphocyte count (ALC) ≥ 200/µL
Other protocol-defined criteria apply.
Exclusion Criteria:
1. History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
2. Active central nervous system involvement
3. History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
4. Ongoing or impending oncologic emergency
5. Recent systemic anti-cancer therapy or radiation
6. Ongoing non-hematologic toxicities due to prior therapy
7. History of allogeneic stem cell or solid organ transplantation
8. Autologous stem cell transplantation within 6 weeks
9. History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no 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) (Cohort 2).
10. Primary immunodeficiency
11. History of autoimmune disease resulting in end organ injury or requiring recent therapy
Other protocol-defined criteria apply.
Inclusion Criteria
Inclusion Criteria:
1. Age 18 years or older
2. Willing and able to provide written informed consent
3. Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
4. Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
5. Relapsed or refractory disease.
6. At least 1 measurable lesion (per Lugano classification)
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/µL
9. Platelet count ≥ 50,000/µL
10. Absolute lymphocyte count (ALC) ≥ 200/µL
Other protocol-defined criteria apply.
1. Age 18 years or older
2. Willing and able to provide written informed consent
3. Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
4. Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
5. Relapsed or refractory disease.
6. At least 1 measurable lesion (per Lugano classification)
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/µL
9. Platelet count ≥ 50,000/µL
10. Absolute lymphocyte count (ALC) ≥ 200/µL
Other protocol-defined criteria apply.
Gender
All
Gender Based
false
Keywords
CAR T-cell
Non-Hodgkin Lymphoma
CD19/20
CD19
CD20
NHL
Diffuse Large B-cell lymphoma
DLBCL
Transformed follicular lymphoma
TFL
Primary mediastinal B-cell lymphoma
PMBCL
Follicular lymphoma Grade 3B
Large cell follicular lymphoma
Aggressive B-cell NHL
Refractory Aggressive B-Cell Lymphoma
Refractory B-Cell Non-Hodgkin Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Cyclophosphamide
Fludarabine
Lymphoma, Follicular
Lymphoma, B-cell
Immunosuppressive Agents
Immunologic Factors
Disease Attributes
Immune System Diseases
Recurrence
PiNACLE
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05826535
Org Class
Industry
Org Full Name
Lyell Immunopharma, Inc.
Org Study Id
LYL314-101
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)
Outcome Measure
Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent
Outcome Time Frame
Baseline to Month 24
Outcome Description
ORR based on Independent Review Committee (IRC) assessment per Lugano criteria
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR)
Outcome Time Frame
Baseline to Month 24
Secondary Outcomes
Outcome Description
Overall response rate (ORR), Complete response rate (CRR), duration of response (DOR), duration of complete response (DOCR), progression free survival (PFS) based on Investigator assessment until a pivotal trial (Phase 2) portion is initiated at which time all scans will be reviewed by an IRC assessment (Cohort 1) per Lugano criteria
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 1: Evaluate the efficacy of ronde-cel
Outcome Description
Proportion of enrolled participants who receive the target dose of ronde-cel
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 1: Evaluate the feasibility of treatment with ronde-cel
Outcome Description
Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent
Outcome Description
ORR based on Investigator assessment per Lugano criteria
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel
Outcome Description
DOR based on IRC assessment and investigator assessment per Lugano criteria
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel
Outcome Description
Time to response (TTR) based on IRC assessment and investigator assessment per Lugano criteria
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel
Outcome Description
PFS based on IRC assessment and investigator assessment per Lugano criteria
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel
Outcome Description
Overall Survival (OS)
Outcome Time Frame
Baseline to Month 72
Outcome Measure
Phase 2: Estimate the efficacy of ronde-cel
Outcome Description
Incidence and severity of TEAEs
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent
Outcome Description
Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel
Outcome Time Frame
Baseline to Month 24
Outcome Measure
Phase 2: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Dennis Cooper
Investigator Email
dcooper@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Immune System --- IMMUNE SYSTEM DISEASES
Cancer --- NEOPLASMS
MeSH Terms
LYMPHOMA, NON-HODGKIN
LYMPHOMA, LARGE B-CELL, DIFFUSE
LYMPHOMA, FOLLICULAR
LYMPHOMA, B-CELL
LYMPHOMA
DISEASE ATTRIBUTES
IMMUNE SYSTEM DISEASES
RECURRENCE
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
FLUDARABINE
CYCLOPHOSPHAMIDE
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS