Study of Rondecabtagene Autoleucel in Aggressive Large B-Cell Lymphoma

May 26, 2026 updated by: Lyell Immunopharma, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

270

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia, 3004
        • Recruiting
        • The Alfred Hospital
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Recruiting
        • Royal Perth Hospital
  • United States
    • California
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California-Irvine Medical Center
        • Contact:
        • Contact:
          • Stefan Ciurea
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:
        • Contact:
          • Akil Merchant
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles (UCLA) Medical Center
        • Contact:
        • Contact:
          • Sarah M. Larson
      • San Diego, California, United States, 92037
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Colorado Blood Cancer Institute
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Recruiting
        • MedStar Georgetown University Hospital
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Augusta University Medical Center
        • Contact:
        • Contact:
          • Locke Bryan
    • Indiana
      • Indianapolis, Indiana, United States, 46237
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
        • Contact:
          • Umar Farooq
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • University Of Louisville Brown Cancer Center
        • Contact:
        • Contact:
          • Hassaan Yasin
    • Louisiana
      • Shreveport, Louisiana, United States, 71130
        • Recruiting
        • Louisiana State University Health Sciences Center
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Corewell Health
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center Hackensack University Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico Comprehensive Cancer Center
        • Contact:
        • Contact:
          • Matthew L. Fero
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10021
        • Recruiting
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Atrium Health Wake Forest Baptist
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Recruiting
        • University of Cincinnati (UC) Physicians Company, LLC
        • Contact:
          • Tahir Latif
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Recruiting
        • Lehigh Valley Topper Cancer Center Institute
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • West Penn Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Recruiting
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75246
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Texas Transplant Institute
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
        • Contact:
          • Boyu Hu
      • Salt Lake City, Utah, United States, 84143
        • Recruiting
        • Intermountain Healthcare
        • Contact:
        • Contact:
          • Bradley Hunter
    • Virginia
      • Norfolk, Virginia, United States, 24502
        • Recruiting
        • Virginia Oncology Associates
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University-Massey Cancer Center
        • Contact:
        • Contact:
          • William Clark
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy
Experimental: Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy
Experimental: Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy
Experimental: Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy
Experimental: Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy
Experimental: Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)
Single dose determined during Phase 1.
Drug: Fludarabine
Conditioning chemotherapy
Drug: Cyclophosphamide
Conditioning chemotherapy
Drug: Rondecabtagene autoleucel (ronde-cel)
CAR T-cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent
Time Frame: Baseline to Month 24
Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR)
Time Frame: Baseline to Month 24
ORR based on Independent Review Committee (IRC) assessment per Lugano criteria
Baseline to Month 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Evaluate the efficacy of ronde-cel
Time Frame: Baseline to Month 24
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
Baseline to Month 24
Phase 1: Evaluate the feasibility of treatment with ronde-cel
Time Frame: Baseline to Month 24
Proportion of enrolled participants who receive the target dose of ronde-cel
Baseline to Month 24
Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent
Time Frame: Baseline to Month 24
Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel
Time Frame: Baseline to Month 24
ORR based on Investigator assessment per Lugano criteria
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel
Time Frame: Baseline to Month 24
DOR based on IRC assessment and investigator assessment per Lugano criteria
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel
Time Frame: Baseline to Month 24
Time to response (TTR) based on IRC assessment and investigator assessment per Lugano criteria
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel
Time Frame: Baseline to Month 24
PFS based on IRC assessment and investigator assessment per Lugano criteria
Baseline to Month 24
Phase 2: Estimate the efficacy of ronde-cel
Time Frame: Baseline to Month 72
Overall Survival (OS)
Baseline to Month 72
Phase 2: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent
Time Frame: Baseline to Month 24
Incidence and severity of TEAEs
Baseline to Month 24
Phase 2: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent
Time Frame: Baseline to Month 24
Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel
Baseline to Month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lyell Immunopharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 9, 2023

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

June 30, 2031

Study Registration Dates

First Submitted

March 24, 2023

First Submitted That Met QC Criteria

April 12, 2023

First Posted (Actual)

April 24, 2023

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 26, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LYL314-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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