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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 9
- 主要终点
- Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)
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.
干预措施: Interleukin-2 (Drug)
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)
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.
干预措施: Interleukin-2 (Drug)
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)
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.
干预措施: Interleukin-2 (Drug)
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)
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.
干预措施: Interleukin-2 (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)
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.
干预措施: Interleukin-2 (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)
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.
干预措施: KITE-439 (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)
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.
干预措施: Cyclophosphamide (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)
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.
干预措施: Fludarabine (Drug)
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)
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.
干预措施: Interleukin-2 (Drug)
Phase 1B: KITE-439
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.
干预措施: KITE-439 (Drug)
Phase 1B: KITE-439
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.
干预措施: Cyclophosphamide (Drug)
Phase 1B: KITE-439
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.
干预措施: Fludarabine (Drug)
Phase 1B: KITE-439
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.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs)
时间窗: First infusion date of KITE-439 up to 21 days
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.
Phase 1B: Objective Response Rate (ORR)
时间窗: Up to 1.4 years
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.
次要结局
- Phase 1B: Percentage of Participants Experiencing Adverse Events(Up to 1.4 years)
- Phase 1B: Progression-Free Survival (PFS)(Up to 1.4 years)
- Phase 1B: Overall Survival(Up to 1.4 years)
- Phase 1B: Duration of Response (DOR)(Up to 1.4 years)
- Phase 1B: Percentage of Participants With Anti-KITE-439 Antibodies(Up to 1.4 years)
- Phase 1B: Levels of E7 TCR T Cells(Up to 1.4 years)
- Phase 1B: Percentage of Participants With Replication-competent Retrovirus (RCR)(Up to 1.4 years)