Clinical Trials /

FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors

NCT03841110

Description:

FT500 is an off-the-shelf, iPSC-derived NK cell product that can bridge innate and adaptive immunity, and has the potential to overcome multiple mechanisms of immune checkpoint inhibitor (ICI) resistance. The preclinical data provide compelling evidence supporting the clinical investigation of FT500 as monotherapy and in combination with ICI in subjects with advanced solid tumors.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors
  • Official Title: FT500 as Monotherapy and in Combination With Immune Checkpoint Inhibitors in Subjects With Advanced Solid Tumors (Phase 1)

Clinical Trial IDs

  • ORG STUDY ID: FT500-101
  • NCT ID: NCT03841110

Conditions

  • Advanced Solid Tumors
  • Lymphoma
  • Gastric Cancer
  • Colorectal Cancer
  • Head and Neck Cancer
  • Squamous Cell Carcinoma
  • EGFR Positive Solid Tumor
  • HER2-positive Breast Cancer
  • Hepatocellular Carcinoma
  • Small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Pancreas Cancer
  • Melanoma
  • NSCLC
  • Urothelial Carcinoma
  • Cervical Cancer
  • Microsatellite Instability
  • Merkel Cell Carcinoma

Interventions

DrugSynonymsArms
FT500FT500 Monotherapy
NivolumabOPDIVOFT500 in Combination with Immune Checkpoint Inhibitor
PembrolizumabKEYTRUDAFT500 in Combination with Immune Checkpoint Inhibitor
AtezolizumabTECENTRIQFT500 in Combination with Immune Checkpoint Inhibitor
CyclophosphamideFT500 Monotherapy
FludarabineFT500 Monotherapy

Purpose

FT500 is an off-the-shelf, iPSC-derived NK cell product that can bridge innate and adaptive immunity, and has the potential to overcome multiple mechanisms of immune checkpoint inhibitor (ICI) resistance. The preclinical data provide compelling evidence supporting the clinical investigation of FT500 as monotherapy and in combination with ICI in subjects with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
FT500 MonotherapyExperimentalFT500 administered once weekly for 3 weeks as a monotherapy
  • FT500
  • Cyclophosphamide
  • Fludarabine
FT500 in Combination with Immune Checkpoint InhibitorExperimentalFT500 administered once weekly for 3 weeks in combination with one of the following immune checkpoint inhibitors: nivolumab, pembrolizumab or atezolizumab.
  • FT500
  • Nivolumab
  • Pembrolizumab
  • Atezolizumab
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Inclusion Criteria:

        1. Diagnosis of the following, as per Regimen Cohort:

        1A. Regimen A: FT500 Monotherapy (Dose Escalation and Expansion): An advanced solid tumor
        malignancy, including lymphoma, in a subject who has failed or refused available
        FDA-approved therapies and is now a candidate for salvage therapy.

        1B. Regimen B: FT500 + ICI (Dose Escalation): An advanced solid tumor malignancy, including
        lymphomas, that has progressed on treatment with at least one ICI (ie, nivolumab,
        pembrolizumab or atezolizumab), in a subject who has also failed or refused other available
        approved therapies and is now a candidate for salvage therapy.

        1C. Regimen B: FT500 + ICI (Dose Expansion): An advanced solid tumor malignancy, including
        lymphomas, in a subject who is currently receiving nivolumab, pembrolizumab or atezolizumab
        per USPI, with disease progression on the ICI.

        2. Provision of signed and dated ICF.

        3. Presence of measurable disease by iRECIST or RECIL criteria, assessed before the start
        of lympho-conditioning and within 28 days prior to Day 1.

        4. Stated willingness to comply with study procedures and duration. 5. Provision of signed
        and dated ICF to agree to participate, at time of withdrawal or completion of this study,
        in Fate Therapeutics' long-term, non-interventional, observation study, FT-003.

        Exclusion Criteria:

        All Subjects:

          1. Females of reproductive potential who are pregnant or lactating, and males or females
             not willing to use a highly effective form of contraception from Screening through the
             end of the study.

          2. ECOG performance status ≥ 2.

          3. Evidence of insufficient organ function as determined by any one of the following:

               1. Neutrophils <1000/µL or platelets <75,000/µL.

               2. Estimated creatinine clearance <50 mL/minute (Cockcroft-gault).

               3. Total bilirubin >2 x upper limit normal (ULN) with the exception of subjects with
                  Gilbert's Syndrome or known liver metastases.

               4. Aspartate aminotransferase (AST) >3 x ULN, or alanine aminotransferase (ALT) >3 x
                  ULN. For subjects with known liver metastases, AST or ALT >5 x ULN.

               5. Oxygen saturation <90% on room air; pulmonary function tests (PFTs) required if
                  symptomatic or prior known impairment - subject will be excluded if diffusing
                  capacity of the lungs for carbon monoxide (DLCO) or forced expiratory volume 1
                  (FEV1) is <50% of predicted for height and age.

               6. Left ventricular ejection fraction (LVEF) <40% (eg by echocardiogram (ECHO) or
                  multi-gated acquisition (MUGA) scan).

          4. Receipt of any biological therapy, chemotherapy, or radiation (except palliative
             radiation) within 2 weeks prior to Day 1. Subjects in Regimen B currently taking an
             ICI must interrupt ICI dosing at least 2 weeks prior to Day 1.

          5. CNS metastases that have not been treated; or treated CNS metastases that have not
             been stable for at least 6 months.

          6. Clinically significant cardiovascular disease, including stroke or myocardial
             infarction within 6 months prior to first study medication; or the presence of
             unstable angina or congestive heart failure of New York Heart Association grade 2 or
             higher.

          7. Currently receiving or likely to require systemic immunosuppressive therapy (eg,
             prednisone >5 mg daily) for any reason from Day -7 to Day 29.

          8. Uncontrolled infections.

          9. Known allergy to the following FT500 components: Albumin (Human) or DMSO.

         10. Presence of any medical or social issues that are likely to interfere with study
             conduct, or may cause increased risk to subject.

             Additional Exclusion Criteria for Regimen B: FT500 + ICI:

         11. Subjects who experienced an ICI-related adverse reaction that resulted in
             discontinuation of the ICI.

         12. Presence or history of autoimmune disease (eg, lupus erythematosus, rheumatoid
             arthritis, Addison's disease, autoimmune disease associated with lymphoma, Crohn's
             disease, ulcerative colitis), except for subjects with isolated vitiligo, atopic
             dermatitis, controlled hypoadrenalism or hypopituitarism, and controlled thyroid
             disease.

         13. Subjects who have received an allograft organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The incidence of subjects with Dose Limiting Toxicities within each dose level cohort.
Time Frame:Day 29
Safety Issue:
Description:This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD). The MTD will be the highest dose level cohort with at most one DLT in six subjects.

Secondary Outcome Measures

Measure:Objective-response rate (ORR)
Time Frame:Day 29 and every 8 weeks thereafter through Day 366
Safety Issue:
Description:Defined as the proportion of subjects who achieve PR or CR at any time on study. Tumor response will be assessed using modified Response Evaluation Criteria In Solid Tumors for immune-based therapeutics (iRECIST) or Response Evaluation Criteria In Lymphomas (RECIL). Only one or the other assessment criterion will be used to measure tumor response. This will depend upon whether solid tumors or lymphomas are being assessed.
Measure:Duration of FT500 persistence
Time Frame:Day 1 through Day 366
Safety Issue:
Description:defined as duration from Day 1 to undetectable levels of FT500 cells per uL blood.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fate Therapeutics

Trial Keywords

  • Advanced Solid Tumor
  • Lymphoma
  • Breast Cancer
  • Head and Neck Cancer
  • Head and Neck
  • Squamous Cell Carcinoma
  • Gastric Cancer
  • Colorectal Cancer
  • Immunotherapy
  • NK cell therapy
  • Melanoma
  • Checkpoint Inhibitor
  • Immune Checkpoint Inhibitor
  • Monoclonal Antibody
  • Cell therapy
  • Cellular therapy
  • nivolumab
  • pembrolizumab
  • atezolizumab

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