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DRUG:

FT538

i
Other names: FT538, CRISPR-edited, iPSC-derived Cellular Immunotherapy, hnCD16/IL-15RF/CD38KO engineered iPSC-derived NK cell therapy
Associations
Company:
Fate Therap, University of Minnesota
Drug class:
CD38 inhibitor, IL-15R stimulant, CD16 agonist
Associations
1m
FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=9, Completed, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Completed
Trial completion • Trial completion date
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD38 (CD38 Molecule)
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CD38 expression
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cyclophosphamide • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • FT538
9ms
Ph1 Study of FT538 Alone and With Vorinostat for Persistent Low-Level HIV Viremia (clinicaltrials.gov)
P1, N=0, Withdrawn, Masonic Cancer Center, University of Minnesota | N=34 --> 0
Enrollment change
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CD4 (CD4 Molecule)
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Zolinza (vorinostat) • FT538
9ms
MT2021-27 FT538 Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (clinicaltrials.gov)
P1, N=33, Suspended, Masonic Cancer Center, University of Minnesota | Recruiting --> Suspended
Trial suspension
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FT538 • enoblituzumab (MGA271)
11ms
FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Dec 2025 --> Jan 2024
Trial primary completion date • Combination therapy
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD38 (CD38 Molecule)
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CD38 expression
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cyclophosphamide • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • FT538
12ms
FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=50 --> 11
Enrollment closed • Enrollment change
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD38 (CD38 Molecule)
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CD38 expression
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cyclophosphamide • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • FT538
1year
Phase I Study of FT538 + Daratumumab for Treatment of r/r AML (ASH 2023)
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.
P1 data • IO biomarker
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IL15 (Interleukin 15) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)
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cyclophosphamide • Darzalex (daratumumab) • fludarabine IV • FT538
1year
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
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FLT3 (Fms-related tyrosine kinase 3) • GLI2 (GLI Family Zinc Finger 2) • IL15 (Interleukin 15) • ANXA5 (Annexin A5) • NKG2D (killer cell lectin like receptor K1)
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TP53 mutation • FLT3 mutation
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Venclexta (venetoclax) • cytarabine • Xospata (gilteritinib) • azacitidine • FT538
1year
FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov)
P1, N=16, Terminated, Fate Therapeutics | Trial completion date: Aug 2025 --> Aug 2023 | Active, not recruiting --> Terminated; This study was terminated by the Sponsor.
Trial completion date • Trial termination • Combination therapy • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
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KRAS mutation • TMB-H • MSI-H/dMMR • NRAS mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • Bavencio (avelumab) • cyclophosphamide • fludarabine IV • FT538
over1year
FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Fate Therapeutics | Recruiting --> Active, not recruiting | N=189 --> 16
Enrollment closed • Enrollment change • Combination therapy • Metastases
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
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KRAS mutation • TMB-H • MSI-H/dMMR • NRAS mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • Bavencio (avelumab) • cyclophosphamide • fludarabine IV • FT538
2years
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)
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.
P1 data • Combination therapy
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IL15 (Interleukin 15)
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cyclophosphamide • Darzalex (daratumumab) • fludarabine IV • FT538
2years
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)
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 demonstrating the potentiating of ADCC while reducing or eliminating the need for LDC in cell therapy.
Combination therapy • IO biomarker
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CD8 (cluster of differentiation 8) • B2M (Beta-2-microglobulin) • CD4 (CD4 Molecule)
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CD38 expression • CD38 positive
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cyclophosphamide • Darzalex (daratumumab) • fludarabine IV • FT538
over2years
FT538 in Combination With Monoclonal Antibodies in Advanced Solid Tumors (clinicaltrials.gov)
P1, N=189, Recruiting, Fate Therapeutics | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
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KRAS mutation • TMB-H • MSI-H/dMMR • NRAS mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • cyclophosphamide • fludarabine IV • FT538
3years
FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=50, Recruiting, Masonic Cancer Center, University of Minnesota | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD38 (CD38 Molecule)
|
CD38 expression
|
cyclophosphamide • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • FT538
3years
Clinical • New P1 trial • Combination therapy
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KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability)
|
KRAS mutation • TMB-H • MSI-H/dMMR • NRAS mutation
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • cyclophosphamide • fludarabine IV • FT538
almost4years
FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=50, Not yet recruiting, Masonic Cancer Center, University of Minnesota
New P1 trial • Combination therapy
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD38 (CD38 Molecule)
|
CD38 expression
|
fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • FT538 • cyclophosphamide intravenous
4years
[VIRTUAL] cGMP Mass Production of FT538, a First-of-Kind, Off-the-Shelf, Multiplexed Engineered Natural Killer Cell Cancer Immunotherapy Derived from a Clonal Master Induced Pluripotent Stem Cell Line (ASH 2020)
The dose‑escalation utilizes a 3+3 design to identify the maximum tolerated dose of three doses of FT538 on Days 1, 8, and 15 as a monotherapy in r/r AML (Regimen A) and in combination with daratumumab (Regimen B) or elotuzumab (Regimen C) in r/r MM. The trial will test up to five FT538 dose levels ranging from 50 million to 1.5 billion cells, and up to 105 patients will be enrolled. The trial is expected to begin patient enrollment in 2020.
Preclinical • IO biomarker
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IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1)
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CD38 expression
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Darzalex (daratumumab) • Empliciti (elotuzumab) • FT538
4years
[VIRTUAL] Triple Gene-Modified iPSC-Derived NK Cells Combined with Daratumumab for Targeted Immunotherapy Against AML (ASH 2020)
To overcome these barriers, we developed a robust genetic editing and manufacturing platform for the uniform engineering and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs)...Previously, we reported on our ability to effectively target multiple myeloma with our FT538 program (the iNK defined below), now FDA approved for clinical trials...Collectively, our results show that utilizing the iNK cell platform to uniformly express hnCD16 and IL15RF combined with complete CD38 KO is an effective strategy to promote effective ADCC against CD38+ cells in the absence of fratricide, and that CD38 KO reprograms NK cells for higher oxidative metabolic fitness for improved persistence and anti-tumor function. Furthermore, we have generated proof-of-concept data supporting triple gene-modified iNK cells combined with dara as a novel AML immunotherapy.
IO biomarker
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CD38 (CD38 Molecule)
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CD38 expression
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Darzalex (daratumumab) • FT516 • FT538
4years
[VIRTUAL] A Phase I Study of FT538, a First-of-Kind, Off-the-Shelf, Multiplexed Engineered, iPSC-Derived NK Cell Therapy As Monotherapy in Relapsed/Refractory Acute Myelogenous Leukemia and in Combination with Daratumumab or Elotuzumab in Relapsed/Refractory Multiple Myeloma (ASH 2020)
FT538 is an investigational, first-of-kind, multiplexed engineered NK cell therapy generated from a clonal master engineered induced pluripotent stem cell (iPSC) line, which can be used as a renewable source for the mass production of off-the-shelf NK cells for broad patient access...Lympho-conditioning consisting of three consecutive days of fludarabine and cyclophosphamide will be administered prior to the first dose of FT538...Key exclusion criteria include active central nervous system disease, need for systemic immunosuppressive therapy, and prior allograft organ transplant. This trial is expected to begin patient enrollment in 2020.
P1 data • Combination therapy • IO biomarker
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CD38 (CD38 Molecule)
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Darzalex (daratumumab) • Empliciti (elotuzumab) • fludarabine IV • FT538 • cyclophosphamide intravenous