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

Gilead Sciences

Status and phase: Terminated; Phase 1

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

Treatments: Drug: Interleukin-2; Drug: KITE-439; Drug: Fludarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03912831

KT-US-478-0401

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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8 participants in 7 patient groups

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439

Phase 1B: KITE-439

Experimental group

Description:

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.

Treatment:

Drug: Interleukin-2

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: KITE-439