FT538 / Fate Therap, University of Minnesota - LARVOL DELTA

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date: Sep 2028 ➔ Aug 2024 | Suspended ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Aug 2024; Product withdrawn from clinical development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

Fate Therapeutics to Present Clinical and Preclinical Data for iPSC Product Platform at the Society for Immunotherapy of Cancer 37th Annual Meeting (GlobeNewswire) - "Fate Therapeutics...announced that the Company will present clinical and preclinical data for the Company’s induced pluripotent stem cell (iPSC) product platform at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting being held in Boston, MA, and virtually, November 8-12, 2022."

P1 data • Preclinical