Clinical Trial 23940

• Overview

  Study Title:

  A Phase 3 Randomized Controlled Trial of Rondecabtagene Autoleucel (LYL314), An Autologous, Dual-Targeting CD19/CD20 CAR T-Cell Product Candidate, Versus Investigator's Choice of CD19 CAR T-Cell Therapy In Patients With Relapsed or Refractory Large B-Cell Lymphoma in the Second-Line Setting (PiNACLE-H2H)

  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.

  Objective:

  The primary objective of the trial is to compare the efficacy of ronde-cel, an investigational CD19/CD20 CAR T-cell therapy, to CD19 CAR T-cell therapies (axi-cel or liso-cel) based on EFS, defined as the time from randomization to death from any cause, disease progression, failure to achieve a response (partial response [PR] or complete response [CR]) by the Day 84 visit following CAR T-cell therapy administration, or start of new anti-lymphoma therapy without documented progression, whichever comes first. Key Secondary Objectives The key secondary objectives of the study are to compare the efficacy of ronde-cel to CD19 CAR T-cell therapies (axi-cel and liso-cel) based on the ORR, CRR, PFS, and overall survival. 3.1.3. Other Secondary Objectives The other secondary objectives of the study are: To assess safety defined as type and frequency of AEs, serious adverse events (SAEs), and laboratory abnormalities To compare the efficacy of ronde-cel to CD19 CAR T-cell therapies based on the duration of response 3.1.4. Exploratory Objectives Exploratory objectives for the study include: To evaluate the PK of ronde-cel, including maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC₀ ₂₈), and cellular persistence (TLast); To evaluate the rate of IgG recovery following CAR T-cell treatment; To assess CD19 and/or CD20 antigen loss at the time of progression; and To evaluate healthcare utilization, including, but not limited to, inpatient hospitalization days, ICU admissions, unscheduled outpatient visits, and use of supportive care interventions (eg, tocilizumab, corticosteroids).

• Treatments

  Therapies:

  Cell Therapy

  Medications:

  Axicabtagene Ciloleucel (Yescarta); Rondecabtagene Autoleucel (); lisocabtagene maraleucel ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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), 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.

• Exclusion Criteria

  Key Exclusion Criteria:
  • 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

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