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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

400

Phase

  • 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 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

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
Intervention / Treatment
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

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

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

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)

January 12, 2026

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

January 1, 2032

Study Registration Dates

First Submitted

September 16, 2025

First Submitted That Met QC Criteria

September 16, 2025

First Posted (Actual)

September 23, 2025

Study Record Updates

Last Update Posted (Actual)

June 8, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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