NY-ESO-1 TCR / National Cancer Institute, Gilead - LARVOL DELTA

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of Southern California | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTAG1B • ER • HER-2 • PD-L1 • PGR

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Southern California | Trial completion date: Apr 2027 ➔ Aug 2027 | Initiation date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTAG1B • ER • HER-2 • PD-L1 • PGR

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Southern California | Trial completion date: Nov 2026 ➔ Apr 2027 | Initiation date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Nov 2025 ➔ Apr 2026

Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTAG1B • ER • HER-2 • PD-L1 • PGR

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Southern California | Trial completion date: Apr 2026 ➔ Nov 2026

IO biomarker • Metastases • Trial completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CTAG1B • ER • HER-2 • PD-1 • PD-L1 • PGR

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Southern California | Trial primary completion date: Mar 2025 ➔ Oct 2025

IO biomarker • Metastases • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CTAG1B • ER • HER-2 • PD-1 • PD-L1 • PGR

A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of Southern California

IO biomarker • Metastases • New P1 trial • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CTAG1B • ER • HER-2 • PD-1 • PD-L1 • PGR

Anti-NY ESO-1 mTCR Peripheral Blood Lymphocytes (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Albert Einstein College of Medicine | N=10 ➔ 3 | Unknown status ➔ Terminated; Due to lack of accrual the study was formally terminated on 01-JUL-2020. Primary Completion and Study Completion Dates have been revised based accordingly based on respective definitions

Enrollment change • Metastases • Trial termination • Oncology • Solid Tumor • CD4 • CD8 • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=9; Active, not recruiting; Sponsor: Roswell Park Cancer Institute; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Fallopian Tube Cancer • Germ Cell Tumors • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Roswell Park Cancer Institute; Trial completion date: Aug 2020 ➔ Dec 2021; Trial primary completion date: Feb 2020 ➔ Dec 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Germ Cell Tumors • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Roswell Park Cancer Institute; Trial primary completion date: Nov 2019 ➔ Feb 2020

Clinical • Combination therapy • Trial primary completion date • Fallopian Tube Cancer • Germ Cell Tumors • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Roswell Park Cancer Institute; Trial primary completion date: Aug 2019 ➔ Nov 2019

Clinical • Combination therapy • Trial primary completion date • Fallopian Tube Cancer • Germ Cell Tumors • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Roswell Park Cancer Institute; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Fallopian Tube Cancer • Germ Cell Tumors • Ovarian Cancer • Peritoneal Cancer • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=12; Not yet recruiting; Sponsor: Roswell Park Cancer Institute

Clinical • Combination therapy • New P1 trial • Fallopian Tube Cancer • Germ Cell Tumors • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

Genetically Modified T Cells and Decitabine in Treating Patients With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P1; N=9; Active, not recruiting; Sponsor: Roswell Park Cancer Institute; Trial completion date: Dec 2021 ➔ Mar 2032; Trial primary completion date: Dec 2020 ➔ Mar 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Germ Cell Tumors • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B

[VIRTUAL] Modeling the efficacy of NY-ESO-1 TCR T cells (letetresgene autoleucel; GSK3377794) in patients with synovial sarcoma: correlations of response with transduced cell kinetics and biomarkers (SITC 2020) - P1 | "While the impact of fludarabine on IL-15 levels has been previously reported, data presented here show a novel, positive correlation between IL-15 levels pre-infusion and response (p=0.0332). IFNγ, IL-6, and IL-2RA levels appear to be promising pharmacodynamic markers. Optimizing dose and LDR may offer opportunities to maximize antitumor efficacy."

Biomarker • Clinical • IO Biomarker • Oncology • Sarcoma • Solid Tumor • CD8 • IFNG • IL15 • IL2RA • IL6

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma. (PubMed, Nat Commun) - P1 | "Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy."

Biomarker • IO biomarker • Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CCR7 • CD8 • CTAG1B • IFNG • IL15 • IL6

[VIRTUAL] Modeling the efficacy of NY-ESO-1 TCR T cells (letetresgene autoleucel; GSK3377794) in patients with synovial sarcoma: correlations of response with transduced cell kinetics and biomarkers (SITC 2020) - P1 | "While the impact of fludarabine on IL-15 levels has been previously reported, data presented here show a novel, positive correlation between IL-15 levels pre-infusion and response (p=0.0332). IFNγ, IL-6, and IL-2RA levels appear to be promising pharmacodynamic markers. Optimizing dose and LDR may offer opportunities to maximize antitumor efficacy."

Biomarker • Clinical • IO biomarker • Oncology • Sarcoma • Solid Tumor • CD8 • IFNG • IL15 • IL2RA • IL6

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Recruiting

Clinical • Enrollment open • Preclinical • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Jul 2017 ➔ Jul 2018

Clinical • Preclinical • Trial primary completion date • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Jul 2018 ➔ Jul 2017

Clinical • Preclinical • Trial primary completion date • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Jul 2017 ➔ Jul 2027

Clinical • Preclinical • Trial primary completion date • Brain Cancer • Breast Cancer • Ependymoma • Hepatocellular Cancer • Hepatology • Liver Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=11; Completed; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Completed; N=43 ➔ 11; Trial completion date: Jul 2028 ➔ Apr 2020; Trial primary completion date: Jul 2027 ➔ Apr 2020

Clinical • Enrollment change • Preclinical • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI)

Clinical • New P2 trial • Preclinical • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=7; Suspended; Sponsor: National Cancer Institute (NCI); N=43 ➔ 7; Recruiting ➔ Suspended

Clinical • Enrollment change • Preclinical • Trial suspension • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer (clinicaltrials.gov) - P2; N=43; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Mar 2015 ➔ Jul 2018

Clinical • Preclinical • Trial primary completion date • Brain Cancer • Breast Cancer • Ependymoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Meningioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PCR