A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy (PiNACLE-H2H)

June 4, 2026 updated by: Lyell Immunopharma, Inc.

A Phase 3 Randomized Controlled Trial of Rondecabtagene Autoleucel , an Autologous, Dual-targeting CD19/CD20 CAR T-Cell Product Candidate, Vs. Investigator's Choice of CD19 CAR T-Cell Therapy in Patients With Relapsed or Refractory Large B-Cell Lymphoma in the Second-line Setting

This Phase 3 study compares rondecabtagene autoleucel (ronde-cel), a dual-targeting CD19/CD20 CAR T-cell therapy, with investigator's choice of CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphoma in the second-line setting.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PiNACLE-H2H is a Phase 3 randomized controlled trial comparing the efficacy and safety of rondecabtagene autoleucel (ronde-cel, formerly known as LYL314) against the currently approved cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T-cell therapies (axicabtagene ciloleucel [axi-cel] or lisocabtagene maraleucel [liso-cel]), in patients with aggressive LBCL that has relapsed or is refractory to first-line anti-CD20 antibody and anthracycline-containing chemotherapy.

Patients will be randomized (1:1) before leukapheresis to receive either:

  • Ronde-cel; or
  • Investigator's choice of axi-cel or liso-cel

Most patients who receive currently approved CD19-directed CAR T-cell therapies, including axi-cel and liso-cel, still experience progressive disease, often due to mechanisms such as CD19 antigen loss or T-cell exhaustion.

Ronde-cel is a novel, autologous, dual-targeting CD19/CD20 CAR T-cell product candidate enriched for CD62L-positive naïve and central memory T cells, which are associated with enhanced proliferation capacity and persistence. Ronde-cel is an "OR"-gated CAR construct that can fully activate upon recognition of either CD19 or CD20, aiming to improve durability of response despite antigen heterogeneity.

Approximately 400 participants will be enrolled. CAR T-cell therapy in both arms will be administered as a single intravenous infusion following fludarabine and cyclophosphamide lymphodepletion. Participants will be followed for 3 years for safety and efficacy, with long-term follow-up extending to 15 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Not yet recruiting
        • Banner MD Anderson Cancer Center
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • Honor Health
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic Arizona
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Not yet recruiting
        • University of Arkansas
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
      • Los Angeles, California, United States, 90095
        • Not yet recruiting
        • University of California, Los Angeles (UCLA)
      • Orange, California, United States, 92868
        • Not yet recruiting
        • University of California, Irvine
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Colorado Blood Cancer Institute
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Not yet recruiting
        • MedStar Georgetown University Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida
      • Orlando, Florida, United States, 32804
        • Not yet recruiting
        • AdventHealth
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Active, not recruiting
        • Northside Hospital
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Not yet recruiting
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Not yet recruiting
        • Northwestern
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Not yet recruiting
        • University of Iowa
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Not yet recruiting
        • University of Kansas Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Not yet recruiting
        • University of Kentucky
      • Louisville, Kentucky, United States, 40202
        • Not yet recruiting
        • University of Louisville Health
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Not yet recruiting
        • Corewell Health
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • Recruiting
        • University of Nebraska Medical Center (UNMC)
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Not yet recruiting
        • Hackensack
    • New York
      • Buffalo, New York, United States, 14263
        • Not yet recruiting
        • Roswell Park Comprehensive Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Recruiting
        • Duke Cancer Institute
      • Winston-Salem, North Carolina, United States, 27157
        • Not yet recruiting
        • Atrium Health Wake Forest Baptist Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Not yet recruiting
        • University of Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Recruiting
        • Oncology Hematology Care Clinical Trials
      • Cleveland, Ohio, United States, 44195
        • Not yet recruiting
        • Cleveland Clinical Taussig Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Not yet recruiting
        • Allegheny Health Network
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI Oncology Partners
    • Texas
      • Austin, Texas, United States, 78704
        • Recruiting
        • St. David's South Austin Medical Center
      • Fort Worth, Texas, United States, 76104
        • Not yet recruiting
        • University of Texas Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Texas Transplant Institute
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • Recruiting
        • Intermountain Healthcare
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Oncology Associates

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. CAR T cell naïve and eligible to receive a CD19 CART-cell therapy

  2. Histologically confirmed large B-cell lymphoma, including the following types defined by (WHO 2022) or International Consensus Classification (2022)

    • Diffuse large B-cell lymphoma (DLBCL)
    • Transformations of indolent B-cell lymphomas (excluding Richter's transformation)
    • DLBCL/High-grade B-cell lymphoma (HGBCL) with MYC and BCL2 rearrangements
    • High-grade B-cell lymphoma (HGBCL) not otherwise specified (HGBCL NOS)
    • Primary mediastinal large B-cell lymphoma (PMBCL)
    • Grade 3B follicular lymphoma/large cell follicular lymphoma (FL3B)
  3. Relapsed or refractory disease after anti-CD20 antibody and anthracycline-containing first-line chemoimmunotherapy
  4. Measurable disease by presence of [18F]-fluorodeoxyglucose PET/CT positive lesion during Screening per Lugano Criteria
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  6. Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

  1. Patients ineligible to receive CD19 CAR T-cell therapy
  2. Primary CNS lymphoma
  3. Patients with primary cutaneous LBCL, human herpes virus-8 positive lymphoma, Burkitt lymphoma, T cell histiocyte-rich lymphoma, or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter's transformation)
  4. Patients with prior history of malignancy, other than aggressive relapsed or refractory LBCL, unless the patient has been free of the disease for ≥ 2 years
  5. Patients with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
  6. Active autoimmune disease requiring ongoing systemic immunosuppressive therapy.

Note: Other protocol defined Inclusion/Exclusion criteria may 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rondecabtagene autoleucel
Biological: rondecabtagene autoleucel
An autologous, dual-targeting CD19/20 CAR T-cell candidate.
Other Names:
  • LYL314
Active Comparator: Investigator's Choice CD19
axicabtagene ciloleucel, lisocabtagene maraleucel
Biological: axicabtagene ciloleucel
An autologous CD19 CAR T-cell therapy
Other Names:
  • Yescarta
  • axi-cel
Biological: lisocabtagene maraleucel
An autologous CD19 CAR T-cell therapy
Other Names:
  • Breyanzi
  • liso-cel

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event free survival
Time Frame: 36 months
The time interval from treatment initiation until the occurrence of a specific event of interest.
36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 36 months
Best Overall Response per Lugano Criteria
36 months
Complete Response Rate
Time Frame: 36 months
Complete Response per Lugano Criteria
36 months
Progression Free Survial
Time Frame: 36 months
The length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
36 months
Overall Survival
Time Frame: 6 years
The length of time from either the date of diagnosis or the start of treatment for a disease, that patients diagnosed with the disease, are still alive.
6 years
Incidence and severity adverse events
Time Frame: 36 months
To assess safety defined as type and frequency of AEs, serious adverse events (SAEs), and laboratory abnormalities.
36 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 12, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2032

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 16, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LYL314-102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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