FH-FOLR1 CAR T cells / Fred Hutchinson Cancer Center - LARVOL DELTA

RG1125765: Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Refractory or Recurrent/Progressive Osteosarcoma, FIERCe Trial (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Jan 2044 ➔ Jan 2029

Trial primary completion date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • FOLR1

Automated, point-of-care manufacturing of FOLR1-directed CAR T cells for the treatment of ovarian cancer (CIMT 2026) - "In conclusion, we developed a robust, rapid, and efficient process for manufacturing anti-FOLR1 CAR T cells. The platform is well-suited for automated and decentralized POC manufacturing and can be adapted for the production of other CAR T cell therapies."

CAR T-Cell Therapy • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Co-expression of extracellular matrix enzymes heparanase or PH-20 augments the anti-tumor efficacy of folate receptor 1-targeting CAR T cells in an ovarian cancer model (AACR 2024) - "In vivo, all anti-FolR1 CAR T cells rejected OV90 tumors and extended survival compared to tumor alone or untransduced T cells (UTD)... The anti-FolR1 CARs boosted with ECM enzymes HPSE or PH-20 demonstrated specific lysis of FolR1-expressing cell lines, improved penetration through ECM-rich matrices in vitro, and accelerated tumor regression in an ovarian cancer model in vivo. Therefore, ECM CARs may help improve clinical outcomes in patients with ovarian tumors."

CAR T-Cell Therapy • Clinical • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • FOLR1 • GPC3 • IL2 • SDC1 • SPAM1 • TNFA

Point-of-care manufacturing of FOLR1-directed CAR T cells for the treatment of ovarian cancer (AACR 2025) - "In conclusion, we developed a robust, rapid, and efficient process for manufacturing anti-FOLR1 CAR T cells. This platform is well-suited for automated and decentralized POC manufacturing and can be adapted for the production of other CAR T cell therapies."

CAR T-Cell Therapy • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Human VH-antibody-based CAR T cells targeting folate receptor-alpha show enhanced persistence and reduced T-cell exhaustion against ovarian cancer. (PubMed, Biomed Pharmacother) - "Human FOLR1-VH CAR T cells demonstrated potent antitumor activity with reduced exhaustion and enhanced persistence. These properties highlight the VH domain as a promising targeting module for next-generation CAR T-cell therapies in ovarian cancer."

IO biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • LAG3 • PD-1

RG1125765: Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Osteosarcoma, FIERCe Trial (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: May 2026 ➔ Jan 2026

Enrollment open • Trial initiation date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • FOLR1

Phase I study of FH FOLR1 CAR T for pediatric patients with FOLR1+/CBFA2T3::GLIS2+ relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1 | "The FOLR1-directed antibody sequence from amatuximab was reformatted in a second-generation lentiviral construct (IgG4 hinge, CD28 transmembrane, 41-BB costimulatory, and CD3ζstimulatory domains) and generated CARTs (FH-FOLR1 CAR T) were evaluated in CBF/GLIS preclinicalmodels...Once the patient has recoveredfrom any acute toxicities from bridging therapy, lymphodepletion (fludarabine/cyclophosphamide) isadministered, followed by infusion of the FH-FOLR1 CAR T on day 0...The primary objectives include assessing thesafety and toxicity, as well as the feasibility of manufacturing the FH-FOLR1 CAR T in children with R/RAML. Secondary objectives include determination of the engraftment and expansion of the FH-FOLR1CAR T in BM, PB and CSF, the persistence in PB, and to determine the preliminary anti-leukemia activityof the CAR T in children with FOLR1+ AML.Trial Status: Enrollment is ongoing at 0.3x106 cells/kg."

Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Pediatrics • CBFA2T3 • CD4 • FOLR1 • GLIS2

RG1125765: Genetically Engineered Cells (FH-FOLR1 ST CAR T Cells) for the Treatment of Advanced Osteosarcoma, FIERCe Trial (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center

New P1 trial • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: Fred Hutchinson Cancer Center | Recruiting ➔ Suspended

Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

FH-FOLR1 Chimeric Antigen Receptor T Cell Therapy for Treating Pediatric Patients With Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • FOLR1