FT538 / Fate Therapeutics, University of Minnesota - LARVOL DELTA

iPSC-derived NK cell therapy induces durable responses in glioblastoma and overcomes resistance via a B7-H3-targeted tri-specific killer engager. (PubMed, Neuro Oncol) - "FT538 exhibits potent tumoricidal activity in 77% of GSC lines (NK-sensitive and moderately sensitive), with curative potential in sensitive models, and demonstrates favorable persistence and tolerability in vivo. B7-H3-targeted TriKE restores NK sensitivity in resistant tumors. These findings provide a strong preclinical rationale for further clinical evaluation of FT538, alone or combined with B7-H3-targeted TriKE, for glioblastoma and other solid tumors."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IL15

FT538, iPSC-Derived NK Cells Are Potent Inducers of Apoptosis in AML Cells and Their Effect Is Synergistic in Combination with Approved Therapeutic Strategies (ASH 2023) - "iPSC-derived NK therapy offers a standardized, off-the-shelf option for NK cell therapies. FT538 iPSC-derived NK cells induce apoptosis in AML cell lines and patient samples in a dose-dependent manner and show a synergistic effect with Venetoclax, Gilteritinib, Azacitidine, and Cytarabine. Therefore, iPSC-derived NK cell therapy may be a promising possibility for AML treatment, particularly for patients resistant to standard therapies."

Combination therapy • IO biomarker • Acute Myelogenous Leukemia • ANXA5 • FLT3 • GLI2 • IL15 • NKG2D

Phase I Study of FT538 + Daratumumab for Treatment of r/r AML (ASH 2023) - P1 | "We hypothesized that the addition of Dara to fludarabine and cyclophosphamide would enhance lymphodepletion and augment ADCC for CD38+ AML leading to better response rates when combined with FT538. FT538 in combination with daratumumab has been tolerated in a highly pre-treated cohort of patients with expected toxicities and a signal of efficacy."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Transplantation • B3GAT1 • IL15

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Masonic Cancer Center, University of Minnesota | N=33 ➔ 1 | Trial completion date: Sep 2028 ➔ Aug 2024 | Suspended ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Aug 2024; Product withdrawn from clinical development

Enrollment change • Platinum resistant • Trial completion date • Trial primary completion date • Trial termination • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

FT538, iPSC-derived NK cells, enhance AML cell killing when combined with chemotherapy. (PubMed, J Cell Mol Med) - "Flow cytometric analysis revealed that FT538 iPSC-NKs induce AML cell death when combined with the AML therapies: cytarabine, venetoclax and gilteritinib. Moreover, cytarabine did not affect FT538 iPSC-NK viability, suggesting that iPSC-derived NK therapies and chemotherapy may be a promising treatment combination. This study provides the basis for further study of iPSC-derived NK cell therapies as a treatment option for high-risk AML patients, particularly those with disease resistant to standard therapies."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL15

FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 ➔ Oct 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD38 • FLT3 • IDH1 • IDH2

Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Masonic Cancer Center, University of Minnesota | N=34 ➔ 0

Enrollment change • Human Immunodeficiency Virus • Infectious Disease • CD4

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=33 | Suspended | Sponsor: Masonic Cancer Center, University of Minnesota | Recruiting ➔ Suspended

Trial suspension • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Trial primary completion date: Dec 2025 ➔ Jan 2024

Combination therapy • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD38 • FLT3 • IDH1 • IDH2

FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Recruiting ➔ Active, not recruiting | N=50 ➔ 11

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD38 • FLT3 • IDH1 • IDH2

FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Fate Therapeutics | Trial completion date: Aug 2025 ➔ Aug 2023 | Active, not recruiting ➔ Terminated; This study was terminated by the Sponsor.

Combination therapy • Metastases • Trial completion date • Trial termination • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • KRAS • MSI • NRAS • TMB

FT538 in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov) - P1 | N=42 | Terminated | Sponsor: Fate Therapeutics | Trial completion date: Aug 2038 ➔ Aug 2023 | Active, not recruiting ➔ Terminated; This study was terminated by the Sponsor.

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Trial completion date: Aug 2023 ➔ Aug 2024 | Initiation date: Jul 2023 ➔ Jul 2024 | Trial primary completion date: Jul 2023 ➔ Jul 2024

Combination therapy • Monotherapy • Trial completion date • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4 • LAMP1

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=33 | Recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Not yet recruiting ➔ Recruiting

Enrollment open • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Fate Therapeutics | Recruiting ➔ Active, not recruiting | N=189 ➔ 16

Combination therapy • Enrollment change • Enrollment closed • Metastases • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Lung Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • KRAS • MSI • NRAS • TMB

FT538 in Subjects With Advanced Hematologic Malignancies (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Fate Therapeutics | Recruiting ➔ Active, not recruiting | N=105 ➔ 42

Combination therapy • Enrollment change • Enrollment closed • Metastases • Monotherapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Initiation date: Mar 2023 ➔ Jul 2023

Combination therapy • Monotherapy • Trial initiation date • Human Immunodeficiency Virus • Infectious Disease • CD4 • LAMP1

iPSC-Derived CD38-Null NK Cells in Combination with CD38-Targeted Antibody: A Dual Therapeutic Strategy to Enable ADCC and Eliminate Host Immune Cells in Multiple Myeloma (ASH 2022) - P1 | "Anti-CD38 therapeutic monoclonal antibodies (mAbs) such as daratumumab (dara) have shown wide application and therapeutic benefit for Multiple Myeloma (MM) patients...To evaluate the effect of anti-CD38 mAb on host lymphocyte reconstitution we used flow cytometry to characterize PBMCs or marrow collected from MM patients after LDC with cytoxan 300 mg/m2 and fludarabine 30 mg/m2 x 3 days either as monotherapy (N = 4) or in combination with dara 16 mg/kg 1 week prior to LDC (Day -11) and weekly thereafter (n = 3) (NCT05182073)...In the presence of anti-CD38 mAb treatment, B2M/CIITA-null FT538 continued to persist while allogeneic NK cells were not detected, while in the study arm that lacked anti-CD38 mAb, B2M/CIITA-null FT538 was eliminated by the persisting allogeneic NK cells (p<0.001). In summary, these data demonstrate the potential to combine off-the-shelf iPSC-derived CD38-null NK cells with anti-CD38 mAb as a novel therapeutic strategy, uniquely..."

Combination therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • B2M • CD4 • CD8

A Phase I Study of FT538, an Off-the-Shelf, Multiplexed-Engineered, iPSC‑Derived NK Cell Therapy in Combination with Daratumumab in Relapsed/Refractory Multiple Myeloma (ASH 2022) - P1 | "In Regimen B, conditioning chemotherapy (fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2) followed by 3 once-weekly doses of FT538 (Days 1, 8, 15 of a 28-d cycle), ranging from 100 million cells/dose up to 1.5 billion cells/dose, are being evaluated using a standard 3 + 3 dose-escalation design. Administration of up to 3 doses of FT538 cells at 100 or 300 million cells/dose in combination with daratumumab is safe and well tolerated without CRS, neurotoxicity, or GvHD. Interim clinical data, including safety and tolerability and initial anti-tumor activity from the ongoing Phase I dose-escalation study of FT538 in combination with daratumumab in R/R MM, will be presented at the conference."

Combination therapy • P1 data • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Leukemia • Multiple Myeloma • Oncology • IL15

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=33 | Suspended | Sponsor: Masonic Cancer Center, University of Minnesota | Initiation date: Jan 2023 ➔ May 2023 | Not yet recruiting ➔ Suspended

Trial initiation date • Trial suspension • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Masonic Cancer Center, University of Minnesota

Combination therapy • Monotherapy • New P1 trial • Human Immunodeficiency Virus • Infectious Disease • CD4 • LAMP1

MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov) - P1 | N=33 | Not yet recruiting | Sponsor: Masonic Cancer Center, University of Minnesota

New P1 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Phase I study of FT538, an iPSC-derived NK cell therapy, with daratumumab in R/R multiple myeloma (YouTube) - "Ravi Vij, MD, MBA...outlines the rationale of a Phase I study evaluating FT538, an off-the-shelf induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell therapy in combination with daratumumab in relapsed/refractory (R/R) multiple myeloma. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA."

Interview • Video

Interim Phase I clinical data of FT538, an off-the-shelf, multiplexed-engineered, iPSC-derived NK cell therapy, combined with monoclonal antibodies in patients with advanced solid tumors (SITC 2022) - P1 | "Treatment consists of two, 29-day treatment cycles, each consisting of 3 days outpatient conditioning chemotherapy (cyclophosphamide 500 mg/m 2 and fludarabine 30 mg/m 2 ), followed by 3 outpatient once-weekly doses of FT538; mAbs are administered at standard dose and schedule...Dose escalation is based on a modified toxicity probability interval algorithm dose-escalation design with a starting dose level of 100 million FT538 cells/dose in combination with avelumab or pembrolizumab in PD-L1-expressing solid tumors; trastuzumab in HER2-expressing tumors; or cetuximab in colorectal cancer, squamous head and neck or lung cancers, or epidermal growth factor receptor-mutated lung cancer...Dose escalation is ongoing. Conclusions Interim clinical data, including safety and tolerability and initial anti-tumor activity, from the ongoing Phase I dose-escalation study of FT538 combined with anti-PD-1/L1 or ADCC-competent mAbs in advanced solid tumors will be presented at the..."

Clinical data • IO biomarker • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • IL15 • PD-L1

iPSC-derived NK cells exhibit potent in vitro and in vivo tumorcidal activity against patient-derived glioblastoma stem cells (GSCs) (SNO 2022) - " We performed pre-clinical studies to characterize the tumoricidal activity of FT573 against glioblastomas. Our results demonstrate great promise of FT538 as a glioblastoma therapy, with plans for translation into a first-in-human clinical trial."

Preclinical • Brain Cancer • Glioblastoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • CASP3 • CD276 • GZMB • IL15