E7 TCR cells / National Cancer Institute, Gilead - LARVOL DELTA

Liquid biopsy detects treatment resistance to T cell receptor (TCR)-T cell therapy (SITC 2025) - P1/2 | "Practical limitations of tumor biopsy acquisition pose a challenge to studying the frequency and timing of these resistance mechanisms.5 6 Conversely, liquid biopsy offers a minimally invasive and easily repeatable method for real-time monitoring of tumors difficult or inaccessible to biopsy.7 8 This study aimed to determine if HLA-A*02:01 damaging mutations previously identified in tumor biopsies from 2 patients treated in a phase I trial of E7 TCR-T cell therapy for HPV-associated cancers could also be detected with liquid biopsy.3Methods Archived plasma specimens collected before and after treatment from each of the 2 patients (Patients 4 and 5) were studied. This method holds promise for prospectively predicting response and monitoring for the development of resistance to TCR-based therapeutics.Ethics Approval The trial was registered on clinicaltrials.gov, trial number NCT02858310. This study was approved by the NIH IRB; approval number 16C0154."

Biopsy • IO biomarker • Liquid biopsy • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2 | N=219 | Completed | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Jul 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • HLA-A

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Christian Hinrichs | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Anal Carcinoma • Cervical Adenocarcinoma • Cervical Cancer • Colorectal Cancer • Gene Therapies • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • HLA-A

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2 | N=180 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • HLA-A

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Jan 2026 ➔ Dec 2024

Trial primary completion date • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • HLA-A • PCR

E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2; N=1; Terminated; Sponsor: National Cancer Institute (NCI); Trial completion date: Apr 2024 ➔ Dec 2021; Suspended ➔ Terminated; Trial primary completion date: Apr 2023 ➔ Dec 2021; Logistical challenges

Trial completion date • Trial primary completion date • Trial termination • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • HLA-A

E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer (clinicaltrials.gov) - P1; N=1; Terminated; Sponsor: National Cancer Institute (NCI); N=180 ➔ 1; Trial completion date: Jan 2027 ➔ Sep 2021; Suspended ➔ Terminated; Trial primary completion date: Jan 2022 ➔ Sep 2021; Multiple logistical challenges

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer • HLA-A

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Jan 2026 ➔ Dec 2020

Trial primary completion date • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • PCR

E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2; N=1; Suspended; Sponsor: National Cancer Institute (NCI); N=180 ➔ 1; Recruiting ➔ Suspended

Enrollment change • Trial suspension • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); N=40 ➔ 180

Enrollment change • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • PCR

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: National Cancer Institute (NCI)

New P1 trial • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • PCR

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Dec 2020 ➔ Jan 2026

Trial primary completion date • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Solid Tumor • Vulvar Cancer • PCR

E7 TCR T Cells for Human Papillomavirus-Associated Cancers (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Phase classification: P1 ➔ P1/2

Phase classification • Gene Therapies • Gynecologic Cancers • Gynecology • Infectious Disease • Oncology • Vulvar Cancer • PCR

E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer (clinicaltrials.gov) - P1; N=180; Suspended; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Suspended

Clinical • Trial suspension • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer (clinicaltrials.gov) - P1; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

A Phase II Study of Neoadjuvant E7 TCR T Cell Immunotherapy for Borderline Resectable and Unresectable Stage I HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: National Cancer Institute (NCI); N=180 ➔ 0; Trial completion date: Dec 2024 ➔ Sep 2020; Recruiting ➔ Withdrawn; Trial primary completion date: Jul 2023 ➔ Sep 2020

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer (clinicaltrials.gov) - P1; N=180; Not yet recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Jan 2022 ➔ Jan 2027

Clinical • Trial completion date • Cervical Cancer • Oncology • Solid Tumor • Uterine Cancer

A Phase II Study of Neoadjuvant E7 TCR T Cell Immunotherapy for Borderline Resectable and Unresectable Stage I HPV-Associated Oropharyngeal Cancer (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Anesthesia • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Pilot Study of E7 TCR T Cell Induction Immunotherapy for Stage IIB-IVA Cervical Cancer (clinicaltrials.gov) - P1; N=180; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • New P1 trial • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer

E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: National Cancer Institute (NCI); N=200 ➔ 0; Trial completion date: Apr 2028 ➔ Jul 2020; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Mar 2025 ➔ Jul 2020

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Chronic Kidney Disease • Gynecologic Cancers • Oncology