Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (ZUMA-6)

Gilead Sciences

Status and phase: Completed; Phase 2; Phase 1

Conditions: Refractory Diffuse Large B Cell Lymphoma

Treatments: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: KTE-C19; Biological: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02926833

KTE-C19-106

Details and patient eligibility

About

The primary objective of phase 1 is to evaluate the safety of KTE-C19 and atezolizumab combination regimens.

The primary objective of phase 2 is to evaluate the efficacy of KTE-C19 and atezolizumab, as measured by complete response rate in participants with refractory diffuse large B-cell lymphoma (DLBCL).

Participants who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968 (NCT05041309).

Enrollment: 37 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Histologically confirmed DLBCL

2. Chemotherapy-refractory disease, defined as one or more of the following:

   • Stable disease (duration of stable disease must be less than or equal to 6 months) or progressive disease as best response to most recent chemotherapy containing regimen
   • Disease progression or recurrence less than or equal to 12 months of prior autologous stem cell transplantation (SCT)

3. Individuals must have received adequate prior therapy including at a minimum:

   • Anti-cluster of differentiate 20 (anti-CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative; and
   • an anthracycline containing chemotherapy regimen

4. At least one measurable lesion per revised International Working Group (IWG) Response Criteria

5. Age 18 years or older

6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1

7. Adequate organ and bone marrow function

8. All individuals or legally appointed representatives/caregivers, must personally sign and date the institutional review board (IRB)/independent ethics committee (IEC) approved consent form before initiating any study specific procedures or activities.

Key Exclusion Criteria:

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
2. History of allogeneic stem cell transplantation
3. Prior CAR therapy or other genetically modified T cell therapy
4. Clinically significant active infection
5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
6. Individuals with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases
7. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
8. History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and participants with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
10. Prior treatment with Programmed Cell Death Ligand 1 (PD-L1) inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of Individuals who received atezolizumab in this study and are eligible for re-treatment
11. Prior CD19 targeted therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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37 participants in 4 patient groups

Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19)

Experimental group

Description:

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide intravenous (IV) infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg followed by 4 doses of atezolizumab (ATZ) (1200 mg/dose) IV infusion every 21 days, beginning 21 days following KTE-C19.

Treatment:

Drug: Cyclophosphamide

Biological: KTE-C19

Biological: Atezolizumab

Drug: Fludarabine

Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19)

Experimental group

Description:

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 14 days following KTE-C19.

Treatment:

Drug: Cyclophosphamide

Biological: KTE-C19

Biological: Atezolizumab

Drug: Fludarabine

Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19)

Experimental group

Description:

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.

Treatment:

Drug: Cyclophosphamide

Biological: KTE-C19

Biological: Atezolizumab

Drug: Fludarabine

Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19)

Experimental group

Description:

Participants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.

Treatment:

Drug: Cyclophosphamide

Biological: KTE-C19

Biological: Atezolizumab

Drug: Fludarabine