Phase 3 Randomized Open‑Label Study of KITE‑753 Versus Axicabtagene Ciloleucel in Relapsed or Refractory Large B‑Cell Lymphoma After First‑Line Therapy

The primary objective is to evaluate the efficacy of KITE‑753 versus axicabtagene ciloleucel in participants with relapsed or refractory large B-cell lymphoma, thereby determining the comparative anti‑tumor activity of the two cellular therapies.

Secondary objectives are to assess:

• Efficacy as measured by objective response rate (ORR).
• Efficacy as measured by progression‑free survival (PFS).
• Efficacy as measured by duration of response and duration of complete remission among responders.
• Safety of KITE‑753 versus axicabtagene ciloleucel.
• Efficacy as measured by overall survival (OS).
• Impact on patient‑reported outcomes and quality of life (QoL) using the H10 instrument.

The trial enrolled 358 adults (≥18 years) of both sexes diagnosed with relapsed or refractory large B-cell lymphoma. Participants were selected from the patient population meeting predefined eligibility, including documented disease relapse or refractoriness within 12 months after initial therapy and at least one measurable tumor at baseline. Eligibility required an Eastern Cooperative Oncology Group performance status of 0‑2, indicating ability to perform daily activities with minimal assistance, and adequate bone‑marrow, renal, hepatic, cardiac, and pulmonary function. Female participants of child‑bearing potential were required to have a negative pregnancy test. The cohort comprised patients classified as vulnerable, reflecting inclusion of individuals who might otherwise be under‑represented, and no additional lifestyle restrictions such as specific diet or exercise regimens were imposed.

The study is a Phase 3, randomized, open‑label, multicenter trial evaluating the efficacy of KITE‑753 versus axicabtagene ciloleucel in participants with relapsed or refractory large B‑cell lymphoma after first‑line therapy; recruitment is planned from September 2026 to May 2031. After an initial screening visit to confirm eligibility criteria—including disease status, measurable tumor, ECOG performance status, organ function, and a negative pregnancy test for women of child‑bearing potential—participants are randomized in a 1:1 ratio to receive a single intravenous infusion of either KITE‑753 or the comparator product. Following infusion, scheduled follow‑up visits are conducted to monitor safety, collect laboratory data, assess tumor response according to the Lugano Classification, and evaluate quality‑of‑life outcomes; the final end‑of‑study visit includes comprehensive efficacy and safety assessments. Participant involvement extends from the screening visit through the end‑of‑study assessment, encompassing the entire follow‑up period defined by the protocol. Early discontinuation may occur if a participant experiences unacceptable toxicity, disease progression that necessitates non‑protocol anti‑lymphoma therapy, or withdraws consent from the study.

The investigational product, KITE-753, is supplied as a dispersion for infusion intended for intravenous administration. The formulation is provided in a single‑dose vial and is administered as an intravenous infusion over a predefined period. The dosing regimen consists of a single infusion of the specified dose; the exact amount is defined in the protocol and is expressed in the study‑specific dosage form unit. Administration occurs under controlled clinical conditions, and the infusion rate is adjusted according to standard safety parameters.

The comparator product, YESCARTA 0.4 – 2 × 10⁸ cells dispersion for infusion, contains the genetically modified autologous T‑cell therapy axicabtagene ciloleucel. It is also delivered as a dispersion for infusion via the intravenous route. Participants receive a single infusion of the cell product, with the target cell dose of 2 × 10⁸ cells per infusion as defined by the study protocol. The infusion is performed under close monitoring in accordance with the product’s prescribing information.

Both study arms require participants to meet the eligibility criteria for relapsed or refractory large B-cell lymphoma following first‑line therapy. The infusion procedures include pre‑medication, vital‑sign monitoring, and observation periods post‑infusion to assess immediate safety. Compliance with the dosing schedule is documented in the case report form, and infusion completion, any interruptions, and adverse events are recorded in real time. Pharmacovigilance assessments and laboratory evaluations are conducted at predefined intervals to ensure adherence to the protocol and to monitor participant safety.

The primary efficacy parameters include a six-month CR rate and Event‑free survival. Complete remission is defined as the proportion of participants achieving CR at Month 6 post‑infusion according to the Lugano Classification, determined by blinded central assessment. Event‑free survival is measured from randomization to the earliest occurrence of death from any cause, disease progression or relapse as assessed centrally, or initiation of any non‑protocol anti‑lymphoma therapy for residual disease. Residual disease assessments are performed by investigators and confirmed by positron emission tomography‑computed tomography or biopsy with pathology review; the timing of the event corresponds to the earliest disease assessment indicating residual disease.

Secondary efficacy endpoints comprise overall response rate, progression‑free survival, duration of response and duration of complete remission, all evaluated by blinded central assessment using the International Working Group Lugano Response Criteria. Overall survival is recorded from randomization until death from any cause. Health‑related quality‑of‑life outcomes are measured by changes from screening to post‑baseline in the European Organisation for Research and Treatment of Cancer QLQ‑C30, the Euro‑QOL EQ‑5D‑5L index and visual analog scale, and the EORTC QLQ‑NHL‑HG29 questionnaires. All efficacy data are collected at scheduled study visits, with imaging and laboratory assessments performed according to the protocol and analyzed centrally.