Study to Evaluate the Safety and Efficacy of KITE-439 in HLA-A*02:01+ Adults With Relapsed/Refractory HPV16+ Cancers

Study Overview
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Brief Summary
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This study has 2 parts: Phase 1A and Phase 1B. The primary objectives of Phase 1A are to evaluate the safety of KITE-439 and to determine a recommended Phase 1B dose. The primary objective of Phase 1B is to estimate the efficacy of KITE-439 in adults who are human leukocyte antigen (HLA)-A*02:01+ and have relapsed/refractory human papillomavirus (HPV)16+ cancers.

Official Title
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A Phase 1 Study Evaluating the Safety and Efficacy of HPV16 E7 T Cell Receptor Engineered T Cells (KITE-439) in HLA-A*02:01+ Subjects With Relapsed/Refractory HPV16+ Cancers

Conditions
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Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer

Intervention / Treatment
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* Drug: KITE-439
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Advanced cancer defined as relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and that is not amenable to definitive locoregional therapy HPV16+ tumor as confirmed by the central laboratory HLA type is HLA-A*02:01+ per local assessment Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Key Exclusion Criteria: Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management Note: Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor Primary immunodeficiency History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years prior to enrollment Known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive), or hepatitis C (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) and/or nucleic acid testing 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, intravenous (IV) infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10^6 E7 T-cell receptor (TCR) T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, subcutaneous (SC) injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 5 × 10^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)<br>Participants will receive conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose is 1 × 10^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<br>|
| Experimental: Phase 1B: KITE-439<br>Participants will receive cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, at a dose selected based on Phase 1A along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | Drug: KITE-439<br>* A single infusion of E7 TCR T cells (KITE-439).<br>Drug: Cyclophosphamide<br>* Administered intravenously.<br>Drug: Fludarabine<br>* Administered intravenously.<br>Drug: Interleukin-2<br>* Administered subcutaneously.<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 Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | A DLT is defined as protocol-defined KITE-439 related Grade 3 events with onset within the first 21 days following KITE-439 infusion and which do not resolve to ≤Grade 2 events within 48 hours, ≥Grade 4 events with onset within the first 21 days following KITE-439 infusion, regardless of duration. | First infusion date of KITE-439 up to 21 days | 
| Phase 1B: Objective Response Rate (ORR) | ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as evaluated by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Up to 1.4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1B: Duration of Response (DOR) | For participants who experience an objective response, DOR was defined as the time from the date of their first objective response to the date of disease progression per modified RECIST v1.1 or death from any cause. | Up to 1.4 years | 
| Phase 1B: Progression-Free Survival (PFS) | PFS was defined as the time from the KITE-439 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause. | Up to 1.4 years | 
| Phase 1B: Overall Survival | Overall survival was defined as the time from KITE-439 infusion to the date of death. | Up to 1.4 years | 
| Phase 1B: Percentage of Participants Experiencing Adverse Events |  | Up to 1.4 years | 
| Phase 1B: Percentage of Participants With Anti-KITE-439 Antibodies |  | Up to 1.4 years | 
| Phase 1B: Percentage of Participants With Replication-competent Retrovirus (RCR) |  | Up to 1.4 years | 
| Phase 1B: Levels of E7 TCR T Cells |  | Up to 1.4 years |