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Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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. Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Colorado Blood Cancer Institute
Denver 5419384, Colorado 5417618 80218

SCRI Oncology Partners
Nashville 4644585, Tennessee 4662168 37203

St. David's South Austin Medical Center
Austin 4671654, Texas 4736286 78704

Intermountain Healthcare
Salt Lake City 5780993, Utah 5549030 84143

Virginia Oncology Associates
Norfolk 4776222, Virginia 6254928 23502

More Details

Status
Recruiting
Sponsor
Lyell Immunopharma, Inc.

Study Contact

Greg Kaufman, MD
000-000-0000
clinicaltrials@lyell.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.