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

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

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.

Study Overview

• Status: Terminated
• Conditions: Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KITE-439; Drug: Interleukin-2

Detailed Description

Participants who received an infusion of KITE-439 will complete the remainder of the 15-year follow-up assessments in a separate Long-term Follow-up study, KT-US-982-5968.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60640
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.
Experimental: 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.	Drug: Cyclophosphamide; Administered intravenously.; Drug: Fludarabine; Administered intravenously.; Drug: KITE-439; A single infusion of E7 TCR T cells (KITE-439).; Drug: Interleukin-2; Administered subcutaneously.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

General Publications

• Kirtane K; Massarelli E; Hanna GJ; et al KITE-439: A Phase 1 Study of HPV16 E7 T Cell Receptor-engineered T Cells in Patients with Relapsed/Refractory HPV16-positive Cancers. ASCO Poster 2020

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2019
• Primary Completion (Actual): February 18, 2022
• Study Completion (Actual): February 18, 2022

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 11, 2019

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Interleukin-2
• Other Study ID Numbers: KT-US-478-0401; 2020-005455-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No