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Large B-cell LymphomaPhase 3PiNACLE-H2HNCT07188558

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

A Phase 3 study testing rondecabtagene autoleucel, axicabtagene ciloleucel and lisocabtagene maraleucel in people with Large B-cell Lymphoma and Lymphoma, B-Cell, run by Lyell Immunopharma, Inc. at 44 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rondecabtagene autoleucel, axicabtagene ciloleucel and lisocabtagene maraleucel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
400 participants
Where
44 sitesin 3 countries
Study dates
12 Jan 2026to Jan 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • CAR T cell naïve and eligible to receive a CD19 CART-cell therapy
  • 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)
Show all 12Show fewer
  • Primary mediastinal large B-cell lymphoma (PMBCL)
  • Grade 3B follicular lymphoma/large cell follicular lymphoma (FL3B)
  • Relapsed or refractory disease after anti-CD20 antibody and anthracycline-containing first-line chemoimmunotherapy
  • Measurable disease by presence of [18F]-fluorodeoxyglucose PET/CT positive lesion during Screening per Lugano Criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Who cannot join

  • Patients ineligible to receive CD19 CAR T-cell therapy
  • Primary CNS lymphoma
  • 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)
  • 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
  • Patients with uncontrolled systemic fungal, bacterial, viral, or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
  • Active autoimmune disease requiring ongoing systemic immunosuppressive therapy.
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

44 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

James Dean, MD, PhD contact

000-000-0000

clinicaltrials@lyell.com

Mary Lessig, MS contact

000-000-0000

clinicaltrials@lyell.com

44 sites in 3 countries

United States41 sites, 41 recruiting

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87102

    Recruiting

  • Northside Hospital

    Atlanta, Georgia, 30342

    Recruiting

  • University of Colorado

    Aurora, Colorado, 80045

    Recruiting

  • St. David's South Austin Medical Center

    Austin, Texas, 78704

    Recruiting

  • Tufts Medical Center

    Boston, Massachusetts, 02111

    Recruiting

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

    Recruiting

  • Northwestern

    Chicago, Illinois, 60611

    Recruiting

  • University of Chicago

    Chicago, Illinois, 60637

    Recruiting

  • Oncology Hematology Care Clinical Trials

    Cincinnati, Ohio, 45242

    Recruiting

  • University of Cincinnati

    Cincinnati, Ohio, 45267

    Recruiting

  • Cleveland Clinical Taussig Cancer Center

    Cleveland, Ohio, 44195

    Recruiting

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

    Recruiting

  • Duke Cancer Institute

    Durham, North Carolina, 27705

    Recruiting

  • University of Texas Southwestern Medical Center

    Fort Worth, Texas, 76104

    Recruiting

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

    Recruiting

  • Hackensack

    Hackensack, New Jersey, 07601

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Recruiting

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

    Recruiting

  • University of Arkansas

    Little Rock, Arkansas, 72205

    Not yet recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Recruiting

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90095

    Recruiting

  • University of Louisville Health

    Louisville, Kentucky, 40202

    Recruiting

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Recruiting

  • Atlantic Health

    Morristown, New Jersey, 07960

    Recruiting

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

    Recruiting

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

    Recruiting

  • University of Nebraska Medical Center (UNMC)

    Omaha, Nebraska, 68105

    Recruiting

  • University of California, Irvine

    Orange, California, 92868

    Recruiting

  • AdventHealth

    Orlando, Florida, 32804

    Recruiting

  • Allegheny Health Network

    Pittsburgh, Pennsylvania, 15212

    Not yet recruiting

  • Virginia Commonwealth University-Massey Cancer Center

    Richmond, Virginia, 23298

    Recruiting

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

    Recruiting

  • Intermountain Healthcare

    Salt Lake City, Utah, 84143

    Recruiting

  • Texas Transplant Institute

    San Antonio, Texas, 78229

    Recruiting

  • Honor Health

    Scottsdale, Arizona, 85258

    Recruiting

  • Mayo Clinic Arizona

    Scottsdale, Arizona, 85259

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Recruiting

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

    Recruiting

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

    Recruiting

  • Atrium Health Wake Forest Baptist Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

    Not yet recruiting

Other trials in United States

Australia2 sites, 2 recruiting

  • Townsville University Hospital

    Douglas, Queensland, 4814

    Recruiting

  • The Alfred

    Melbourne, Victoria, 3004

    Recruiting

Other trials in Australia

Canada1 site, 1 recruiting

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2C4

    Recruiting

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
rondecabtagene autoleucel, axicabtagene ciloleucel, lisocabtagene maraleucel
Keywords
Lymphoma, Non-Hodgkin Lymphoma, CAR T-Cell Therapy, CD19, CD19/CD20, Large B-cell Lymphoma
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rondecabtagene autoleucelBiological

    Also called LYL314

    An autologous, dual-targeting CD19/20 CAR T-cell candidate.

  • axicabtagene ciloleucelBiological

    Also called Yescarta, axi-cel

    An autologous CD19 CAR T-cell therapy

  • lisocabtagene maraleucelBiological

    Also called Breyanzi, liso-cel

    An autologous CD19 CAR T-cell therapy

Study groups in NCT07188558
Study groupRoleWhat they receive
Rondecabtagene autoleucelExperimentalNot described
Receives: Biological: rondecabtagene autoleucel
Investigator's Choice CD19Active comparatoraxicabtagene ciloleucel, lisocabtagene maraleucel
Receives: Biological: axicabtagene ciloleucel; Biological: lisocabtagene maraleucel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event free survival

    The time interval from treatment initiation until the occurrence of a specific event of interest.

    Measured: 36 months

Secondary outcomes (5)

  1. Overall Response Rate

    Best Overall Response per Lugano Criteria

    Measured: 36 months

  2. Complete Response Rate

    Complete Response per Lugano Criteria

    Measured: 36 months

  3. Progression Free Survial

    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.

    Measured: 36 months

  4. Overall Survival

    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.

    Measured: 6 years

  5. Incidence and severity adverse events

    To assess safety defined as type and frequency of AEs, serious adverse events (SAEs), and laboratory abnormalities.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2025
  2. Study start12 Jan 2026
  3. Primary completionDec 2029 (estimated)
  4. Study completionJan 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07188558
Sponsor's protocol ID
LYL314-102
Acronym
PiNACLE-H2H
Status last verified
Nov 2026
First submitted
16 Sep 2025
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rondecabtagene autoleucel, axicabtagene ciloleucel and lisocabtagene maraleucel in people with Large B-cell Lymphoma and Lymphoma, B-Cell, run by Lyell Immunopharma, Inc. at 44 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact James Dean, MD, PhD (000-000-0000, clinicaltrials@lyell.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event free survival (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07188558.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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