FATE-NK100 as Monotherapy and in Combination With Monoclonal Antibody in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1, single-dose, open-label, dose-escalation study. The study will be conducted in three parts (i.e. regimens) in an outpatient setting as follows: Regimen A: FATE-NK100 as a monotherapy in subjects with advanced solid tumor malignancies. Regimen B: FATE-NK100 in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, HER2+ advanced gastric cancer or other advanced HER2+ solid tumors. Regimen C: FATE-NK100 in combination with cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC), or other epidermal growth factor receptor 1 positive (EGFR1+) advanced solid tumors.

Official Title
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FATE-NK100 as Monotherapy and in Combination With Monoclonal Antibody in Subjects With Advanced Solid Tumors

Conditions
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HER2 Positive Gastric Cancer, Colorectal Cancer, Head and Neck Squamous Cell Carcinoma, EGFR Positive Solid Tumor, Advanced Solid Tumors, HER2-positive Breast Cancer, Hepatocellular Carcinoma, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Pancreatic Cancer, Melanoma

Intervention / Treatment
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* Drug: FATE-NK100
* Drug: Cetuximab
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Regimen A only (monotherapy): Subjects with advanced metastatic solid tumors Regimen B only (combination with trastuzumab): Subjects with advanced metastatic HER2+ solid tumors Regimen C only (combination with cetuximab): Subjects with advanced metastatic EGFR+ solid tumors Available related donor who is CMV+ and HLA-haploidentical or better but not fully HLA-matched Presence of measurable disease by RECIST 1.1 Life expectancy of at least 3 months. Provision of signed and dated informed consent form (ICF). Stated willingness to comply with study procedures and duration. Exclusion Criteria: Females of reproductive potential that 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. Eastern Cooperative Oncology Group (ECOG) performance status >2. Evidence of insufficient organ function as determined by the protocol. Receipt of any biological therapy, chemotherapy, or radiation within 1 week of the Screening Visit and at least 3 weeks prior to Day 1, except for patients receiving maintenance trastuzumab. Have central nervous system disease (CNS) as follows: Dose Escalation Cohorts: Active CNS disease, including history of CNS metastases. MTD/MFD Expansion Cohorts: CNS disease, including history of CNS metastases, that was not stable during the last 6 months. Myocardial infarction (MI) within 6 months of Screening Visit. Severe asthma. Currently receiving or likely to require systemic immunosuppressive therapy from Day -7 to Day 29. Uncontrolled infections. Presence of any medical or social issues that are likely to interfere with study conduct, or may cause increased risk to subject.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>FATE-NK100 as a monotherapy in subjects with advanced solid tumor malignancies. | Drug: FATE-NK100<br>* FATE-NK100 is a donor-derived NK cell product comprised of ex vivo activated effector cells with enhanced anti-tumor activity<br>|
| Experimental: Regimen B<br>FATE-NK100 in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, HER2+ advanced gastric cancer or other advanced HER2+ solid tumors. | Drug: FATE-NK100<br>* FATE-NK100 is a donor-derived NK cell product comprised of ex vivo activated effector cells with enhanced anti-tumor activity<br>Drug: Trastuzumab<br>* HER2/neu receptor inhibitor<br>* Other names: Herceptin;|
| Experimental: Regimen C<br>Regimen C: FATE-NK100 in combination with cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC), or other epidermal growth factor receptor 1 positive (EGFR1+) advanced solid tumors. | Drug: FATE-NK100<br>* FATE-NK100 is a donor-derived NK cell product comprised of ex vivo activated effector cells with enhanced anti-tumor activity<br>Drug: Cetuximab<br>* Epidermal growth factor receptor inhibitor antineoplastic agent<br>* Other names: Erbitux;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) | The incidence of dose-limiting toxicity (DLT) within each dose cohort within the first 28 days after FATE-NK100 administration (ie, Day 1 through Day 29). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective-response rate (ORR) | Objective-response rate (ORR): defined as the proportion of patients who achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time on study. | 28 days, 57 days, 113 days, 169 days, 225 days, 281 days, 337 days, and 366 days. | 
| Pharmacokinetics (PK) of FATE-NK100 | The PK of FATE-NK100, as assessed by the proportion of lymphocytes in peripheral blood that are of donor/product origin at the specified time points. | 0 days, 1 day, 3 days, 5 days, 8 days, 12 days, 15 days, 22 days, 29 days, 43 days, 57 days, 85 days, 113 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Squamous Cell Carcinoma, Gastric Cancer, HER2 Positive, EGFR Positive, EGFR+, HER2+, Immunotherapy, NK cell therapy, Natural killer cell therapy, antibody-dependent cell-mediated cytotoxicity, ADCC, Non small cell lung cancer, Renal cancer, Solid Tumor, HER2, EGFR, Advanced Solid Tumor, Breast Cancer, Head and Neck Cancer, Colorectal Cancer