KITE-439: A phase I study of HPV16 E7 T cell receptor-engineered T cells in patients with relapsed/refractory HPV16-positive cancers.

Authors

null

Kedar Kirtane

Moffitt Cancer Center, Tampa, FL

Kedar Kirtane , Erminia Massarelli , Glenn J. Hanna , Christopher Austin Klebanoff , George Blumenschein Jr., Michael Russell Bishop , Sylvia Lee , Jiaxin Niu , Sabina Adhikary , Stephanie H. Astrow , Katherine Rodriguez , Rong Chu , A. Scott Jung

Organizations

Moffitt Cancer Center, Tampa, FL, City of Hope National Medical Center, Duarte, CA, Dana-Farber Cancer Institute, Boston, MA, Memorial Sloan Kettering Cancer Center, New York, NY, The University of Texas MD Anderson Cancer Center, Houston, TX, University of Chicago Medicine, Chicago, IL, Fred Hutchinson Cancer Research Center, Seattle, WA, Banner MD Anderson Cancer Center, Gilbert, AZ, Kite, a Gilead Company, Santa Monica, CA

Research Funding

Pharmaceutical/Biotech Company
Kite, a Gilead Company

Background: Human papillomavirus 16 (HPV16) is the most prominent subtype across invasive head and neck cancers, as well as cervical cancer and other anogenital cancers (Saraiya M, et al. J Natl Cancer Inst. 2015). The HPV16 E7 (E7) viral antigen is important for the survival of HPV-positive tumor cells but is absent from normal human tissue, making it an attractive target for anti-cancer therapy. Preclinical efficacy has been observed with MHC class I-restricted T cell receptor (TCR)-engineered T cells targeting E7 on HPV16-positive tumor cells (Jin BY, et al. JCI Insight. 2018). This Phase 1, first-in-human, open-label, multicenter study (NCT03912831) will evaluate the safety and efficacy of KITE-439, an autologous TCR-engineered T cell therapy targeting E7, in HLA-A*02:01–positive patients with relapsed/refractory HPV16-positive cancers. Methods: A single-patient dose-escalation schema will be used in Phase 1A of the study, enrolling up to 30 patients. Phase 1A will evaluate safety and inform the recommended dose of KITE-439 for Phase 1B. Approximately 45 patients with squamous cell cancer of the head and neck, cervical cancer, and other HPV16-positive tumors will be included in Phase 1B. Patients in Phase 1A and Phase 1B may receive optional bridging therapy followed by cyclophosphamide and fludarabine conditioning chemotherapy. Patients will then receive an infusion of KITE-439 at 1 × 106 up to 1 × 108 TCR-transduced T cells/kg along with daily subcutaneous IL-2 therapy for a maximum of 14 doses post-infusion. The primary endpoint for Phase 1A is the incidence of adverse events defined as dose-limiting toxicities. The primary endpoint for Phase 1B is investigator-assessed objective response rate per modified RECIST v1.1 criteria (Eisenhauer EA, et al. Eur J Cancer. 2009). Secondary endpoints for Phase 1B include duration of response, progression-free survival, overall survival, and safety. Patients ≥ 18 years must be HLA-A*02:01–positive and have relapsed/refractory HPV16-positive cancer, an ECOG PS of ≤ 1, and adequate bone marrow and organ function. Key exclusion criteria include a history of stroke, myocardial infarction, or symptomatic deep vein thrombosis/pulmonary embolism, known infection with human immunodeficiency virus, detectable hepatitis C, or detectable hepatitis B. This study is currently open and accruing patients. Clinical trial information: NCT03912831.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Cellular Immmunotherapy

Clinical Trial Registration Number

NCT03912831

Citation

J Clin Oncol 38: 2020 (suppl; abstr TPS3149)

DOI

10.1200/JCO.2020.38.15_suppl.TPS3149

Abstract #

TPS3149

Poster Bd #

213

Abstract Disclosures