FT516 in Combination With Monoclonal Antibodies in Advanced Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: FT516; Drug: IL-2; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Avelumab

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center/John Theurer Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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
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
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

Collaborators and Investigators

• Sponsor: Fate Therapeutics
• Investigators: Study Director: Fate Trial Disclosure, Fate Therapeutics

Publications and helpful links

General Publications

• Zhu H, Blum RH, Bjordahl R, Gaidarova S, Rogers P, Lee TT, Abujarour R, Bonello GB, Wu J, Tsai PF, Miller JS, Walcheck B, Valamehr B, Kaufman DS. Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity. Blood. 2020 Feb 6;135(6):399-410. doi: 10.1182/blood.2019000621.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): August 11, 2023
• Study Completion (Actual): August 11, 2023

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; PD-L1; urothelial cancer; renal cell carcinoma; cellular therapy; immune checkpoint inhibitor; NK cells; triple negative breast cancer; merkel cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Aldesleukin; Cyclophosphamide; Avelumab; Fludarabine
• Other Study ID Numbers: FT516-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No