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This is a Phase I dose-finding study of FT576 as monotherapy and in combination with the monoclonal antibody daratumumab in multiple myeloma (MM). The study will consist of a dose-escalation stage and an expansion stage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimens A-A4 | Experimental | FT576 single dose monotherapy in subjects with r/r MM |
|
| Regimen A1 | Experimental | FT576 multiple dose monotherapy in subjects with r/r MM |
|
| Regimens B-B4 | Experimental | FT576 single dose in combination with daratumumab in subjects with r/r MM |
|
| Regimen B1 | Experimental | FT576 multiple dose in combination with daratumumab in subjects with r/r MM |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FT576 (Allogenic CAR NK cells with BCMA expression) | Drug | Experimental Interventional Therapy: FT576 comprises allogeneic natural killer (NK) cells, derived from a clonal, CD38-knockout, human-induced pluripotent stem cell line (iPSC) that expresses anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR), high-affinity, non-cleavable CD16 (hnCD16), and IL-15/IL-15 receptor fusion protein (IL-15RF). |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and nature of DLTs within each dose-escalation cohort to determine the MTD or MAD | Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1 | |
| Determine the RP2D which will be based on the overall safety and anti-tumor activity among the dose escalation and dose expansion cohorts | From FPI to LPI's end of Cycle 1 study treatment (End of cycle is Day 29 from Day 1 FT576 infusion) | |
| Incidence, nature, and severity of adverse events | Cycle 1 Day -5 to Day 29 for Regimen A and A1; Cycle 1 Day -11 to Day 29 (each cycle is 40 days) for Regimen B and B1 |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | Proportion of subjects with a best overall response of sCR, CR, VGPR, or PR, as determined by the investigator according to standard IMWG response criteria | From baseline tumor assessment up to approximately 2 years after last dose of FT576 |
| Duration of response (DOR) |
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Diagnosis of r/r MM with measurable disease by at least one of the following:
Note: for all Regimens, prior BCMA CAR T-cell therapy and BCMA-targeted therapy (e.g., bi-specific engagers or antibody-drug conjugates) is allowed
* Abbreviated exclusion criteria:
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2
Evidence of insufficient hematologic function:
Evidence of insufficient organ function
Clinically significant cardiovascular disease:
Subjects with active central nervous system (CNS) , including leptomeningeal disease. Subjects with prior CNS involvement may be enrolled into the study if effective treatment of their CNS disease was completed at least 3 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging.
Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
Currently receiving or likely to require immunosuppressive therapy (e.g., prednisone >5 mg daily) for any reason during the treatment period, with the exception of inhaled corticosteroids.
Clinically significant infections, including:
Live vaccine <6 weeks prior to start of conditioning
Receipt of an allograft organ transplant
Ongoing requirement for systemic graft -versus-host disease therapy
Plasma cell leukemia defined as a plasma cell count >2000/mm^3
Prior malignancy (other than current indication including any antecedent hematologic disorder) within the 2 years prior to enrollment except for the following: basal or squamous cell carcinomas of the skin, carcinoma in situ of the cervix or breast treated with curative intent, or localized prostate cancer treated with curative intent, or malignancy that, in the opinion of the investigator and Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years.
Washout periods from prior therapies:
- Chemotherapy, or radiation therapy, except for palliative purposes, within 14 days prior to the first dose of FT576 (Day 1) or five half-lives, whichever is shorter; Investigational therapy within 30 days prior to the first dose of FT576 study treatment or five half-lives, whichever is shorter; Biologic therapy (e.g., anti-CD38 mAbs or anti-SLAMF7 monoclonal antibodies), including autologous cellular immunotherapy (e.g. CAR-T/ CAR-NK), antibody-drug conjugates or bi-specific immune-cell engaging antibody within 30 days prior to first dose of FT576 (Day 1) or half -lives whichever is shorter. prior allogenic HSCT or allogenic CAR-T/CAR-NK within 6 months of first dose of FT576 (Day1).
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| Name | Affiliation | Role |
|---|---|---|
| Fate Trial Disclosure | Fate Therapeutics, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35205 | United States | ||
| City of Hope |
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| Label | URL |
|---|---|
| ASH Dec 2020 Abstract | View source |
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|
| Cyclophosphamide | Drug | Conditioning Agent |
|
| Fludarabine | Drug | Conditioning Agent |
|
| Daratumumab | Drug | Anti-CD38 Monoclonal Antibody |
|
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| Bendamustine | Drug | Conditioning Agent |
|
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Duration from the first occurrence of a documented objective response until the time of disease progression or relapse, or death due to progressive disease, as determined by the investigator according to standard IMWG response criteria |
| Up to 15 years |
| Progression-free survival (PFS) | Time from first dose of study treatment to disease progression or relapse, or to the day of death from any cause, as determined by the investigator according to standard IMWG response criteria | Up to 15 years |
| Relapse-free survival (RFS) from complete response (CR) | Duration from the start of sCR or CR until the time of relapse from sCR or CR, as determined by the investigator according to standard IMWG response criteria | Up to 15 years |
| Overall survival (OS) | Time from first dose of study treatment to death from any cause | Up to 15 years |
| Pharmacokinetics (PK) of FT576 | Concentration of FT576 in peripheral blood following FT576 administration | From Baseline to PTFU visit of last cycle on the study treatment (End of cycle is Day 29 from Day 1 FT576 infusion of this cycle) |
| Duarte |
| California |
| 91010 |
| United States |
| Scri-Cbci | Denver | Colorado | 80218 | United States |
| Medical Oncology Hematology Consultants | Newark | Delaware | 19713 | United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| University of Minnesota | Saint Paul | Minnesota | 55108 | United States |
| Washington University | St Louis | Missouri | 63130 | United States |
| Roswell Park | Buffalo | New York | 14263 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| Oncology Hematology Care, Inc | Cincinnati | Ohio | 45226 | United States |
| Tennessee Oncology - Nashville | Nashville | Tennessee | 37203 | United States |
| Texas Oncology-Medical City Dallas | Dallas | Texas | 75230 | United States |
| Virginia Oncology Associates | Norfolk | Virginia | 23502 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C556306 | daratumumab |
| D000069461 | Bendamustine Hydrochloride |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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