Clinical Trial 24189

• Overview

  Study Title:

  A Phase 3, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of KITE-753 Versus Axicabtagene Ciloleucel in Participants with Relapsed or Refractory Large B-Cell Lymphoma After First-Line Therapy

  Summary:

  The goal of this clinical study is to compare the study drug KITE-753 versus axicabtagene ciloleucel (axi-cel) in adult participants with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) after one prior line of therapy. The primary objective of this study is to evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel.

  Objective:

  Primary Objectives: To evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel Secondary Objectives: To evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel, as measured by ORR To evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel, as measured by PFS To evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel, as measured by DOR and duration of CR among responding participants To evaluate the safety of KITE-753 versus axicabtagene ciloleucel To evaluate the efficacy of KITE-753 versus axicabtagene ciloleucel on OS To evaluate the efficacy of KITE-753 on patient-reported outcomes and QoL versus axicabtagene ciloleucel Exploratory Objectives: To evaluate the efficacy of KITE-753 using ctDNA MRD To evaluate the pharmacokinetics, pharmacodynamics, and biomarkers of response and resistance to treatment of KITE-753 and axicabtagene ciloleucel To evaluate the composite safety and efficacy of KITE-753 versus axicabtagene ciloleucel, as measured by TFPFS-12 To evaluate the composite safety and efficacy of KITE-753 versus axicabtagene ciloleucel, as measured by TFPFS-18 To evaluate the composite efficacy and safety of KITE-753 versus axicabtagene ciloleucel, as measured by TFCR-3 To evaluate the composite efficacy and safety of KITE-753 versus axicabtagene ciloleucel, as measured by TFCR-6

• Treatments

  Therapies:

  Autologous CAR T-cell therapy; anti-CD19/CD20 CAR T-cell product

  Medications:

  Axicabtagene Ciloleucel (Yescarta); KITE-753 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Individuals with any of the following large B-cell lymphomas, as determined by the investigator.
  • Individuals with relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapsed ≤ 12 months of completion of first-line therapy.
  • Note: If the relapse is confirmed by imaging per International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma within 12 months, the confirmatory biopsy must be performed within 90 days of the 12-month cutoff.
  • Prior therapy must have included an anti-CD20 antibody (including CD20-targeting T-cell engager antibodies) and an anthracycline-containing chemotherapy regimen.
  • For individuals with transformed indolent NHL, therapies given for non-transformed disease do not count as a line of therapy for the transformed disease.
  • Individuals who have had no additional systemic therapy or holding therapy (except for steroids and/or local radiation) following first-line therapy and prior to leukapheresis are eligible.
  • At least 1 measurable lesion according to the IWG Lugano Response Criteria. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. A measurable lesion is defined as >1.5 cm longest transverse diameter (LDi) for lymph node and > 1.0 cm LDi for extranodal lesion. Splenomegaly or hepatomegaly alone in the absence of a measurable lesion is not considered to be measurable disease.
  • Toxicities due to immediate prior therapy must have recovered to Grade 1 or lower (except for clinically nonsignificant toxicities such as alopecia, unless otherwise specified in the protocol).
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • Adequate bone marrow function.
  • Adequate renal, hepatic, cardiac, and pulmonary function.
  • Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test (females who have undergone surgical sterilization or have been postmenopausal for at least 2 years before randomization are not considered to be of childbearing potential.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Prior CAR T-cell therapy or other cell-based therapy.
  • History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease-free and without anti-cancer therapy (with the exception of hormonal therapy in the case of breast cancer) for at least 3 years. Individuals with asymptomatic localized low-grade prostate cancer for which a watch-and-wait approach is standard of care are eligible.
  • Individuals with the following LBCL fifth edition of WHO criteria subtypes: Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, T-cell/histiocyte-rich LBCL, mediastinal gray zone lymphoma, plasmablastic lymphoma, intravascular LBCL, primary central nervous system (CNS) lymphoma, primary vitreoretinal LBCL, fibrin-associated LBCL, fluid overload-associated LBCL lymphomatoid granulomatosis, high-grade B-cell lymphoma (HGBCL) with 11q aberrations, anaplastic lymphoma kinase-positive LBCL, LBCL with Interferon Regulatory Factor 4 (IRF4) rearrangement, and transformed from Hodgkin's lymphoma (HL). Note: Individuals with primary testicular LBCL are eligible.
  • History of a severe, immediate hypersensitivity reaction attributed to aminoglycosides
  • Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management. Note: Simple urinary tract infections and uncomplicated bacterial or viral upper respiratory tract infections are permitted if the individual is responding to active treatment and satisfies the criteria of being afebrile for 48 hours (ie, temperature > Known history of hepatitis B virus (HBV) (hepatitis B surface (HBs) antigen (HBsAg) positive) infection, or hepatitis C (anti-hepatitis C virus (HCV)) positive) infection. History of a hepatitis B or C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) or nucleic acid testing. Note: Individuals who are seropositive for HBV (ie, HBs and/or hepatitis B core antibody positive) are eligible if they are HBsAg-negative and negative for viral DNA. Individuals who are seropositive because of HBV vaccination are eligible (ie, HBs antibody positive, hepatitis core antibody-negative, and HBsAg-negative). Individuals on prophylactic and suppressive antiviral medications against HBV and/or HCV administered per institutional or clinical practice guidelines are eligible.
  • HIV-positive, unless taking appropriate anti-HIV medications, with an undetectable viral load by qPCR and a CD4 count ≥ 200 cells/μL. Note: HIV-positive individuals in Australia are not permitted regardless of active antiretroviral therapy or undetectable blood viral load.
  • History or presence of the following CNS disorders: hemorrhage, dementia (per CTCAE v5.0 Grade 2 or higher memory impairment), cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema with confirmed structural defects by appropriate imaging.
  • History of stroke or transient ischemic attack within 6 months before enrollment. Individuals with seizure disorders requiring active anticonvulsive medication.
  • Individuals with cardiac atrial or cardiac ventricular lymphoma involvement.
  • Individuals with secondary CNS lymphoma.
  • Individuals with full thickness lymphoma involvement of gastric or intestinal lining. Individuals with concern for gastric or intestinal perforation or known contained perforation.
  • Other protocol defined Inclusion/Exclusion criteria may apply.

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