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

NCT03912831 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: KT-US-478-0401
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Phase 1B: Duration of Response (DOR)

  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: 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

Study Arms (7)

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

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

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

Phase 1B: KITE-439

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2

Interventions

KITE-439 DRUG

A single infusion of E7 TCR T cells (KITE-439).

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1); Phase 1A: 1 x 10^7 KITE-439 (Cohort 3); Phase 1A: 1 x 10^8 KITE-439 (Cohort 5); Phase 1A: 1 x 10^8 KITE-439 (Cohort 6); Phase 1A: 3 x 10^6 KITE-439 (Cohort 2); Phase 1A: 3 x 10^7 KITE-439 (Cohort 4); Phase 1B: KITE-439

Cyclophosphamide DRUG

Administered intravenously.

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1); Phase 1A: 1 x 10^7 KITE-439 (Cohort 3); Phase 1A: 1 x 10^8 KITE-439 (Cohort 5); Phase 1A: 1 x 10^8 KITE-439 (Cohort 6); Phase 1A: 3 x 10^6 KITE-439 (Cohort 2); Phase 1A: 3 x 10^7 KITE-439 (Cohort 4); Phase 1B: KITE-439

Fludarabine DRUG

Administered intravenously.

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1); Phase 1A: 1 x 10^7 KITE-439 (Cohort 3); Phase 1A: 1 x 10^8 KITE-439 (Cohort 5); Phase 1A: 1 x 10^8 KITE-439 (Cohort 6); Phase 1A: 3 x 10^6 KITE-439 (Cohort 2); Phase 1A: 3 x 10^7 KITE-439 (Cohort 4); Phase 1B: KITE-439

Interleukin-2 DRUG

Administered subcutaneously.

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1); Phase 1A: 1 x 10^7 KITE-439 (Cohort 3); Phase 1A: 1 x 10^8 KITE-439 (Cohort 5); Phase 1A: 1 x 10^8 KITE-439 (Cohort 6); Phase 1A: 3 x 10^6 KITE-439 (Cohort 2); Phase 1A: 3 x 10^7 KITE-439 (Cohort 4); Phase 1B: KITE-439

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (9)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60640, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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

  RESULT

MeSH Terms

Conditions

Papillomavirus Infections; Neoplasms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 11, 2019
• Study Start: April 30, 2019
• Primary Completion: February 18, 2022
• Study Completion: February 18, 2022
• Last Updated: December 26, 2023
• Results First Posted: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)