Study of KITE-363 or KITE-753 in Participants With Relapsed and/or Refractory B-cell Lymphoma

Gilead Sciences

Status and phase: Enrolling; Phase 1

Conditions: Relapsed and/or Refractory B-cell Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: KITE-363; Biological: KITE-753

Study type: Interventional

Funder types: Industry

Identifiers

NCT04989803

KT-US-499-0150

2020-000562-41 (EudraCT Number)

Details and patient eligibility

About

The goal of this clinical study is to learn more about the safety and dosing of the study drugs, KITE-363 and KITE-753, in participants with relapsed and/or refractory B-cell lymphoma.

Full description

Eligible study participants who have received IP administration with either KITE-363 or KITE-753 will transition to a separate Long-term Follow-up study (Study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Enrollment: 114 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Relapsed and/or refractory B-cell lymphoma (R/R BCL).
• At least 1 measurable lesion.
• Adequate organ and bone marrow (BM) function.

Key Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease free and without anticancer therapy (with the exception of hormonal therapy in the case of breast cancer) for at least 3 years.
• History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
• History of allogeneic stem cell transplant (allo-SCT).
• Auto-SCT within 6 weeks before the planned KITE-363 or KITE-753 infusion.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management.
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) hepatitis B surface (HBs) antigen (HBsAg) positive infection, or hepatitis C (anti-hepatitis C virus [HCV] positive) infection.
• Individuals with detectable cerebrospinal fluid (CSF) malignant cells or brain metastases or a history of central nervous system (CNS) lymphoma, primary CNS lymphoma, or spinal epidural involvement.
• History or presence of a CNS disorder.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmia, New York Heart Association Class II or greater congestive heart failure or other clinically significant cardiac disease within the 6 months before enrollment.
• Primary immunodeficiency.
• History of autoimmune disease resulting in or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 2 years.
• History of non-line associated, clinically significant deep-vein thrombosis or pulmonary embolism requiring therapeutic anticoagulation within the 6 months before enrollment.
• Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of childbearing potential.

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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114 participants in 2 patient groups

KITE-363

Experimental group

Description:

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-363 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-363. 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-363 at 1 or more dose-level deemed to be tolerable.

Treatment:

Biological: KITE-363

Drug: Fludarabine

Drug: Cyclophosphamide

KITE-753

Experimental group

Description:

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-753 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-753. 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-753 at 1 or more dose-level deemed to be tolerable.

Treatment:

Biological: KITE-753

Drug: Fludarabine

Drug: Cyclophosphamide