FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 dose-finding study of FT-516 in combination with monoclonal antibodies in participants with advanced solid tumors. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

Official Title
-----------------
A Phase I, Open-Label, Multicenter Study of FT516 in Combination With Monoclonal Antibodies in Subjects With Advanced Solid Tumors

Conditions
-----------------
Solid Tumor, Adult

Intervention / Treatment
-----------------
* Drug: FT516
* Drug: Avelumab
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: IL-2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Locally advanced or metastatic solid tumor malignancies that have relapsed or progressed after at least one line of therapy and where the following anti-PD-L1 are approved: avelumab, atezolizumab or durvalumab Capable of giving signed informed consent Aged ≥ 18 years old Willingness to comply with study procedures and duration Measurable disease per iRECIST Contraceptive use for women and men as defined in the protocol Exclusion Criteria: Pregnant or breast-feeding women ECOG performance status ≥ 2 Evidence of insufficient organ function Clinically significant cardiovascular disease Receipt of therapy within 2 weeks prior to Day 1 or five half-lives, whichever is shorter or any investigational therapy within 28 days prior to Day 1 Known active central nervous system (CNS) involvement by malignancy Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease or receipt of medications for these conditions Currently receiving or likely to require immunosuppressive therapy Known active infections with Hepatitis B, Hepatitis C or HIV Live vaccine within 6 weeks prior to start of lympho-conditioning Known allergy to albumin (human) or DMSO

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FT516 in combination with avelumab<br> | Drug: FT516<br>* Experimental Interventional Therapy<br>Drug: Avelumab<br>* Monoclonal antibody<br>* Other names: Bavencio;Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>Drug: IL-2<br>* Biologic response modifier<br>* Other names: Aldesleukin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose-Limiting Toxicities (DLTs) Within Each Dose Level Cohort | The incidence of DLTs within each dose level cohort will be reported. A DLT is any adverse event (AE) that is at least possibly related to FT516 that occurs after the first FT516 infusion through the end of the DLT assessment period on Cycle 1 Day 29, and meets 1 of the criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 or the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading Guidelines for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. | Up to Day 29 after the end of Cycle 1 (each cycle is 28 days) | 
| Severity of DLTs Within Each Dose Level Cohort | The severity of DLTs within each cohort will be reported. DLT is any adverse event (AE) that is at least possibly related to FT516 that occurs after the first FT516 infusion through the end of the DLT assessment period on Cycle 1 Day 29, and meets 1 of the criteria from the NCI CTCAE v5.0 or the ASTCT Consensus Grading Guidelines for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. | At the end of Cycle 1 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with ≥1 Adverse Events (AE) | An AE is any untoward medical occurrence in a participants temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to 15 years | 
| Investigator-Assessed Duration of Response (DOR) | DOR is the time from the first occurrence of a documented, objective response until the time of disease progression, relapse or death from any cause, whichever occurs first, per modified Response Evaluation Criteria in Solid Tumors (iRECIST) response criteria. | Up to 15 years | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants with Stable Disease more than 6 months, Partial Response or Complete Response, per iRECIST response criteria. | Up to 15 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from first dose of lympho-conditioning to disease progression or to the day of death for any reason, whichever occurs first, per iRECIST response criteria. | Up to 15 years | 
| Overall Survival (OS) | OS is defined as the time from first dose of lympho-conditioning to death from any cause. | Up to 15 years | 
| Determination of PK of FT516 in peripheral blood | The pharmacokinetics of FT516 in peripheral blood will be reported as the relative percentage of product (FT516) DNA versus patient DNA (% chimerism) measured from blood samples at the specified time points | Study Days 1, 2, 4, 8, 11, 18, 22, 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PD-L1, cellular therapy, NK cells, urothelial cancer, renal cell carcinoma, merkel cell carcinoma, non-small cell lung cancer, NSCLC, triple negative breast cancer, immune checkpoint inhibitor