EGFR806-specific CAR T-cell therapy / Seattle Children's Hospital, Cellevolve Bio, Seattle Children’s Therapeutics - LARVOL DELTA

STRIvE-01: EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Seattle Children's Hospital | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2025 ➔ Jun 2040

Enrollment closed • Trial primary completion date • Brain Cancer • Ewing Sarcoma • Eye Cancer • Germ Cell Tumors • Hepatoblastoma • Nephrology • Neuroblastoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Retinal Disorders • Retinoblastoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Wilms Tumor • EGFR

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Seattle Children's Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Multiplex ddPCR Platform for Precision Monitoring of Multi-Antigen CAR T Cells in Pediatric CNS Cancer Therapy (ASGCT 2025) - P1 | "While our BrainChild-03 (BC-03, NCT04185038) demonstrated tolerability of intracerebroventricular (ICV) delivery of B7-H3 CAR T cells for diffuse intrinsic pontine glioma (DIPG), efficacy was inconsistent...The assay characterized CAR representation and transduction patterns in BrainChild-04 infusion products (n=31), (Figure 1c), detecting FLAP-EF1 at 2.00 ± 0.26 copies/ng, with individual CARs detected as follows: B7H3 (0.577 ± 0.11), EGFR806 (0.366 ± 0.07), HER2 (0.536 ± 0.09), and IL13zetakine (0.440 ± 0.07)... Amplitude multiplex ddPCR is a robust platform for multi-antigen CAR quantification, offering critical insights into CAR T cell persistence in pediatric CNS tumors after ICV delivery. Ongoing correlative analysis from the BC-04 trial will further validate its utility. Combining VCN-based ddPCR with multiparameter flow cytometry enhances understanding of CAR T cell dynamics, guiding future therapy design, dosing strategies, and..."

CAR T-Cell Therapy • Clinical • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • CD276 • EGFR • HER-2

Locoregional Infusion of EGFR806-CAR T Cells for Recurrent or Refractory Pediatric CNS Tumors: Results of the Completed BrainChild02 Phase 1 Clinical Trial. (PubMed, Neuro Oncol) - "Intracranially infused EGFR806-CAR T cells were tolerable at tested doses, with a best response of stable disease. EGFR is a potentially useful target for cellular therapy against pediatric brain tumors, particularly high-grade gliomas."

Journal • P1 data • Brain Cancer • CNS Disorders • CNS Tumor • Diffuse Midline Glioma • Epilepsy • Glioma • Malignant Glioma • Oncology • Pain • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor • EGFR

EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors (clinicaltrials.gov) - P1 | N=11 | Completed | Sponsor: Seattle Children's Hospital | Active, not recruiting ➔ Completed | Trial completion date: Mar 2040 ➔ Dec 2023 | Trial primary completion date: Mar 2025 ➔ Dec 2023

CAR T-Cell Therapy • IO biomarker • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioma • Medulloblastoma • Oncology • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • EGFR

STRIvE-01: EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Seattle Children's Hospital | Trial completion date: Jun 2038 ➔ Jun 2040 | Trial primary completion date: Jun 2024 ➔ Jun 2025

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Ewing Sarcoma • Eye Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Hepatoblastoma • Hepatology • Nephrology • Neuroblastoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Retinal Disorders • Retinoblastoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Wilms Tumor • EGFR

STRIvE-01: EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: Seattle Children's Hospital | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial primary completion date • Brain Cancer • CNS Tumor • Ewing Sarcoma • Eye Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Hepatoblastoma • Hepatology • Nephrology • Neuroblastoma • Neuroendocrine Tumor • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Retinal Disorders • Retinoblastoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Wilms Tumor • EGFR

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Seattle Children's Hospital | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Seattle Children's Hospital

CAR T-Cell Therapy • New P1 trial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Seattle Children's Hospital | Recruiting ➔ Active, not recruiting | N=36 ➔ 11

Enrollment change • Enrollment closed • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioma • Medulloblastoma • Oncology • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • EGFR

[VIRTUAL] High affinity chimeric antigen receptor with cross-reactivity to clinically-relevant EGFR mutated proteins (SNO 2020) - P1 | "To study this further We generated two structurally different CARs by fusing the scFv of mAb806 to 4-1BB and Killer immunoglobulin like receptor (KIR) co-stimulatory domains...Unlike EGFR-specific cetuximab based CAR, EGFR-806CART cells did not kill EGFR wild type expressing fetal brain primary astrocytes and keratinocytes in vitro...The broad specificity of EGFR806 CART cells to amplified EGFR and its mutant variants gives us the potential to clear various forms of EGFR. The enhanced anti-tumor efficacy by KIR based CAR in vivo setting provides us with additional therapeutic options."

Clinical • Glioblastoma • Graft versus Host Disease • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • EGFR

STRIvE-01: Phase I study of EGFR806 CAR T-cell immunotherapy for recurrent/refractory solid tumors in children and young adults. (ASCO 2022) - P1 | "All subjects received lymphodepleting chemotherapy with fludarabine and cyclophosphamide prior to the administration of cryopreserved CAR T cells a the prescribed dose level. EGFR806 directed CAR-T cells have an acceptable toxicity profile in CYA with R/RST and demonstrate anti-tumor activity in some patients. Additional analyses are ongoing to identify biomarkers of response and toxicity."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Fatigue • Hepatology • Inflammation • Oncology • Pain • Pediatrics • Solid Tumor • NTRK

EGFR as a potent CAR T target in triple negative breast cancer brain metastases. (PubMed, Breast Cancer Res Treat) - "Our results demonstrates anti-tumor activity of EGFR806 CAR T cells against TNBC cells in vitro and in vivo. Given EGFR806 CAR T cells are currently undergoing clinical trials in primary brain tumor patients without obvious toxicity, our results are immediately actionable against the TNBC-BM patient population."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EGFR

EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Seattle Children's Hospital; Trial completion date: Jun 2036 ➔ Jun 2038; Trial primary completion date: Jun 2021 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • Ewing Sarcoma • Eye Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Hepatoblastoma • Hepatology • Nephrology • Neuroblastoma • Neurofibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Retinal Disorders • Retinoblastoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • CD19 • EGFR

EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Seattle Children's Hospital; Trial completion date: Mar 2037 ➔ Mar 2040; Trial primary completion date: Mar 2022 ➔ Mar 2025

Clinical • IO biomarker • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Germ Cell Tumors • Glioma • Medulloblastoma • Oncology • Pediatrics • Pineoblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor