Study of KITE-197 in Participants With Relapsed or Refractory Large B-cell Lymphoma

Study Overview
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Brief Summary
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This study will have two Phases: Phase 1a and Phase 1b. The goal of Phase 1a of this clinical study is to learn more about the safety, tolerability and dosing of study drug KITE-197, in participants with relapsed or refractory large B-cell lymphoma (r/rLBCL). The goal of Phase 1b of this clinical study is learn about the effectiveness of the recommended dose of KITE-197 in participants with r/r LBCL. The primary objectives of this study are: Phase 1a: To evaluate the safety of KITE-197 in participants with r/r LBCL and determine the target dose level for Phase 1b. Phase 1b: To evaluate the efficacy of KITE-197 in participants with r/r LBCL as measured by the complete remission (CR) rate.

Detailed Description
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Participants will be followed for approximately 24 months after the infusion of KITE-197 before transitioning to a separate Kite long-term follow-up study KT-US-982-5968, in which they will be followed for the remainder of the 15-year follow-up period.

Official Title
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A Phase 1 Open-label, Single Arm, Multicenter Study Evaluating the Safety and Efficacy of KITE-197 in Subjects With Relapsed or Refractory Large B-cell Lymphoma

Conditions
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Relapsed/Refractory Large B-cell Lymphoma

Intervention / Treatment
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* Drug: KITE-197
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Relapsed or Refractory Large B-cell Lymphoma At least 1 measurable lesion Adequate organ and bone marrow function Key Exclusion Criteria: History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 2 years History of Richter's transformation of chronic leukemic lymphoma History of allogenic stem cell transplant (SCT) Autologous SCT within 6 weeks of planned KITE-197 infusion Prior CD19 targeted antibody, such as tafasitamab and loncastuximab with the exception of individuals who have previously achieved an objective response to such therapy and their tumor expresses CD19 by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (IHC) at the time of screening. Individuals who meet these criteria may be eligible Prior treatment with bendamustine within 6 months of enrollment Prior CAR therapy or other genetically modified cell therapy Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management History of HIV infection or acute or chronic active hepatitis B or C infection History or presence of a clinically significant central nervous system (CNS) disorder Note: Prior or active CNS involvement by lymphoma is not an exclusion criterion. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrollment Presence of primary immunodeficiency History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism within 3 months before enrollment. Catheter induced DVT which has been treated for at least 6 weeks prior to enrollment is permitted Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KITE-197<br>Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-197 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-197. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-197 CAR-transduced autologous T cells at 1 or more dose-level deemed to be tolerable. | Drug: KITE-197<br>* A single infusion of CAR-transduced autologous T cells administered intravenously<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy administered intravenously<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) |  | First infusion date of KITE-197 up to 28 days | 
| Phase 1b: Complete Remission (CR) Rate | Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Adverse Events (AEs) |  | Enrollment up to 24 months plus 30 days | 
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) |  | Enrollment up to 24 months plus 30 days | 
| Overall Response Rate (ORR) | ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma therapy, per the Lugano Classification, as determined by the investigator. | Up to 24 months | 
| Duration of Response (DOR) | DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator. | Up to 24 months | 
| Progression-Free Survival (PFS) | PFS is defined as the time from KITE-197 infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause. | Up to 24 months | 
| Event Free Survival (EFS) | EFS is defined as the time from KITE-197 infusion to the earliest occurrence of death due to any cause, disease progression/relapse per investigator, or initiation of new anti-lymphoma therapy. | Up to 24 months | 
| Time to Next Treatment (TTNT) | TTNT is defined as time from KITE-197 infusion to the start of subsequent new lymphoma therapy or death from any cause. | Up to 24 months | 
| Overall Survival (OS) | OS is defined as the time from KITE-197 infusion to death from any cause. | Up to 24 months | 
| Number of KITE-197 CAR T Cells in Blood Over Time Post Infusion |  | Up to 24 months | 
| Proportion of Immune Cell Subsets in KITE-197 |  | Up to 24 months |