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

NCT ID: NCT07188558

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2032-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Large B-cell Lymphoma Lymphoma, B-Cell Relapsed Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Non-Hodgkin Lymphoma Non-Hodgkin Lymphoma Refractory/ Relapsed Diffuse Large B Cell Lymphoma (DLBCL) Diffuse Large B Cell Lymphoma Refractory Diffuse Large B Cell Lymphoma Relapsed

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rondecabtagene autoleucel

Group Type EXPERIMENTAL

rondecabtagene autoleucel

Intervention Type BIOLOGICAL

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

Investigator's Choice CD19

axicabtagene ciloleucel, lisocabtagene maraleucel

Group Type ACTIVE_COMPARATOR

axicabtagene ciloleucel

Intervention Type BIOLOGICAL

An autologous CD19 CAR T-cell therapy

lisocabtagene maraleucel

Intervention Type BIOLOGICAL

An autologous CD19 CAR T-cell therapy

Interventions

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rondecabtagene autoleucel

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

Intervention Type BIOLOGICAL

axicabtagene ciloleucel

An autologous CD19 CAR T-cell therapy

Intervention Type BIOLOGICAL

lisocabtagene maraleucel

An autologous CD19 CAR T-cell therapy

Intervention Type BIOLOGICAL

Other Intervention Names

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LYL314 Yescarta axi-cel Breyanzi liso-cel

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lyell Immunopharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status NOT_YET_RECRUITING

Honor Health

Scottsdale, Arizona, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status NOT_YET_RECRUITING

University of Arkansas

Little Rock, Arkansas, United States

Site Status NOT_YET_RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

University of California, Irvine

Orange, California, United States

Site Status NOT_YET_RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status NOT_YET_RECRUITING

University of Miami

Miami, Florida, United States

Site Status NOT_YET_RECRUITING

AdventHealth

Orlando, Florida, United States

Site Status NOT_YET_RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status NOT_YET_RECRUITING

Northside Hospital

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Northwestern

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status NOT_YET_RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status NOT_YET_RECRUITING

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status NOT_YET_RECRUITING

University of Kentucky

Lexington, Kentucky, United States

Site Status NOT_YET_RECRUITING

University of Louisville Health

Louisville, Kentucky, United States

Site Status NOT_YET_RECRUITING

Corewell Health

Grand Rapids, Michigan, United States

Site Status NOT_YET_RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status NOT_YET_RECRUITING

University of Nebraska Medical Center (UNMC)

Omaha, Nebraska, United States

Site Status NOT_YET_RECRUITING

Hackensack

Hackensack, New Jersey, United States

Site Status NOT_YET_RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status NOT_YET_RECRUITING

Duke Cancer Institute

Durham, North Carolina, United States

Site Status NOT_YET_RECRUITING

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status NOT_YET_RECRUITING

Oncology Hematology Care Clinical Trials

Cincinnati, Ohio, United States

Site Status NOT_YET_RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status NOT_YET_RECRUITING

Cleveland Clinical Taussig Cancer Center

Cleveland, Ohio, United States

Site Status NOT_YET_RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

St. David's South Austin Medical Center

Austin, Texas, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center

Fort Worth, Texas, United States

Site Status NOT_YET_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Texas Transplant Institute

San Antonio, Texas, United States

Site Status NOT_YET_RECRUITING

Intermountain Healthcare

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status RECRUITING

Swedish Cancer Institute

Seattle, Washington, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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David Shook, MD

Role: CONTACT

000-000-0000

Mary Lessig, MS

Role: CONTACT

000-000-0000

Other Identifiers

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LYL314-102

Identifier Type: -

Identifier Source: org_study_id

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