First-in Cancer-Type Phase I Study of FT536 for Recurrent WHO Grade 4 Astrocytoma

This is a single center, first-in cancer-type phase I clinical trial of FT536 for adult patients with recurrent WHO Grade 4 astrocytoma, irrespective of IDH-mutational status, for which a standard of care repeat craniotomy for gross tumor resection at time of first or second recurrence is achievable. Per this treatment schema, FT536 will be administered once intratumorally

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Astrocytoma; Progressive Disease
• Intervention / Treatment: Biological: FT536; Procedure: Biopsy/ Intratumoral Injection/ Gross Tumor Resection; Diagnostic test: Blood/ Cerebrospinal Fluid/ Tumor Pathology

Detailed Description

This is a single center, first-in cancer-type phase I clinical trial of FT536 for adult patients with recurrent WHO Grade 4 astrocytoma, irrespective of IDH-mutational status, for which a standard of care repeat craniotomy for gross tumor resection at time of first or second recurrence is achievable.

Per this treatment schema, FT536 will be administered once intratumorally. FT536 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human induced pluripotent stem cell (iPSC) line with the following four engineered elements: a) deletion of the gene encoding CD38 (i.e., CD38 knockout); b) expression of the MICA and MICB (MICA/B) chimeric antigen receptor (CAR); c) high-affinity, non-cleavable CD16 receptor; and d) an interleukin (IL)-15/IL15 receptor alpha fusion protein.

Current neuro-oncology professional census accepts the practice of a 2-stage neurosurgical intervention when there are radiographic changes concerning for recurrent cancer. First, the region of radiographic concern is biopsied to histologically confirm recurrence versus pseudoprogression. If intraoperative pathology is consistent with recurrence, then FT536 will be injected with a total volume of 1 mL infused along the biopsy tract into the residual enhancing portion, but also into the nonenhancing portions if safe and feasible per the discretion of the operating neurosurgeon. Occurring 7- 14 days later, the patient will undergo maximum safe surgical resection and a post-operative safety MR brain imaging will be performed to assess neurosurgical outcome and potential local toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Elizabeth C. Neil, MD
      • Contact: Elizabeth C. Neil, MD; Phone Number: 612-273-8383; Email: neile@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed WHO Grade 4 astrocytoma from archival tissue. IDH mutation status and MGMT promoter methylation status will not limit candidacy but needs to be known.
• Evidence of first or second cancer recurrence/ progression by magnetic resonance imaging (MRI) for which a gross tumor resection (GTR) is feasible as determined by the primary investigator in concordance with the study-affiliated neurosurgeon.
• Previous completed SOC antitumor treatment including surgery, radiation therapy, and temozolomide +/- Optune/ Tumor Treatment Fields (TTF).
• No concurrent alternative curative therapy, including use of TTF.
• Able to undergo standard MRI scans with contrast agent throughout the course of the study.
• ≥ 18 years and ≤ 75 years of age at the time of consent.
• Karnofsky performance status ≥70.
• Must be completely off or on a dose of dexamethasone 2mg daily or less with stable neurological function at the time of enrollment.
• Adequate organ function within 14 days of study treatment start as defined in Section 4.1.9 of the protocol.
• Participants of childbearing potential (POCBP) or with partners of childbearing potential must use a highly effective form of contraception from the time of the screening visit until at least 3 months after the dose of FT536.
• Must agree to and sign the consent for the companion Long-Term Follow-Up study (CPRC# 2021LS077).
• Voluntary written consent prior to the performance of any research related procedures.
• Agree to stay in the Twin Cities metropolitan area (i.e. within a 45-minute drive of the UMN) from the time of biopsy through hospital discharge following completion of the planned craniotomy.

Exclusion Criteria:

• Clinically significant increased intracranial pressure (e.g., impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures or any other situation requiring urgent neurosurgical intervention.
• History of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/ AML.
• Radiographic evidence of leptomeningeal disease.
• Received prior treatment with bevacizumab or any other cellular therapy available on or off a clinical trial.
• Non-malignant CNS disease such as CNS vasculitis or neurodegenerative disease.
• Prior or current GammaTile, Gliadel wafer use, or other implanted therapeutic agent or photodynamic therapy.
• Any known condition that requires systemic immunosuppressive therapy - inhaled and topical steroids are permitted.
• Pregnant or breastfeeding. Menstruating POCBP must have a negative pregnancy test within 14 days before the planned biopsy. Patient must agree to use highly effective method of birth control from the time of the screening visit until at least 3 months after the dose of FT536.
• Known seropositive for HIV or known Hepatitis B or C infection with detectable viral load by PCR.
• Prior history of malignancy within 5 years of enrollment other than basal or squamous cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of the breast, or prostate cancer treated with surgery or RT with a prostate specific antigen of <0.01 ng/mL tested within 28 days of trial enrollment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pec

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level Cohort -1; FT536 1 x 10^7 cells/dose. Used only if excess toxicity encountered on dose level 1.	Biological: FT536; FT536 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human induced pluripotent stem cell (iPSC) line with the following four engineered elements: a)deletion of the gene encoding CD38 (i.e., CD38 knockout); b) expression of the MICA andMICB (MICA/B) chimeric antigen receptor (CAR); c) high-affinity, non-cleavable CD16 receptor; and d) an interleukin (IL)-15/IL15 receptor alpha fusion protein.; Procedure: Biopsy/ Intratumoral Injection/ Gross Tumor Resection; On Study Day 1, the region of radiographic concern is biopsied to histologically confirm cancer recurrence versus pseudoprogression. If intraoperative pathology is consistent with cancer recurrence, then FT536 will be injected with a total volume of 1 mL infused via a ventricular catheter placed along the biopsy tract. Occurring between Study Day 8-15, the patient will undergo maximum safe surgical resection; Diagnostic test: Blood/ Cerebrospinal Fluid/ Tumor Pathology; Blood analysis will occur throughout the study to determine the quality of endogenous NK cells and T cells as well as cytokine concentrations. Cerebrospinal fluid sampling will occur at 2-3 time points throughout the study and the fluid will be analyzed for cytokines and immune cells. Compare pre- (from biopsy) versus post- (from resection) injection pathology to determine FT536 motility, replication ability, and impact on the microenvironment as well as malignant astrocytoma cell death plus the persistence of endogenous NK cells
Experimental: Dose Level Cohort 1; FT536 2 x 10^7 cells/dose	Biological: FT536; FT536 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human induced pluripotent stem cell (iPSC) line with the following four engineered elements: a)deletion of the gene encoding CD38 (i.e., CD38 knockout); b) expression of the MICA andMICB (MICA/B) chimeric antigen receptor (CAR); c) high-affinity, non-cleavable CD16 receptor; and d) an interleukin (IL)-15/IL15 receptor alpha fusion protein.; Procedure: Biopsy/ Intratumoral Injection/ Gross Tumor Resection; On Study Day 1, the region of radiographic concern is biopsied to histologically confirm cancer recurrence versus pseudoprogression. If intraoperative pathology is consistent with cancer recurrence, then FT536 will be injected with a total volume of 1 mL infused via a ventricular catheter placed along the biopsy tract. Occurring between Study Day 8-15, the patient will undergo maximum safe surgical resection; Diagnostic test: Blood/ Cerebrospinal Fluid/ Tumor Pathology; Blood analysis will occur throughout the study to determine the quality of endogenous NK cells and T cells as well as cytokine concentrations. Cerebrospinal fluid sampling will occur at 2-3 time points throughout the study and the fluid will be analyzed for cytokines and immune cells. Compare pre- (from biopsy) versus post- (from resection) injection pathology to determine FT536 motility, replication ability, and impact on the microenvironment as well as malignant astrocytoma cell death plus the persistence of endogenous NK cells
Experimental: Dose Level Cohort 2; FT536 6 x 10^7 cells/dose	Biological: FT536; FT536 is an allogeneic natural killer (NK)-cell immunotherapy produced from a clonal master human induced pluripotent stem cell (iPSC) line with the following four engineered elements: a)deletion of the gene encoding CD38 (i.e., CD38 knockout); b) expression of the MICA andMICB (MICA/B) chimeric antigen receptor (CAR); c) high-affinity, non-cleavable CD16 receptor; and d) an interleukin (IL)-15/IL15 receptor alpha fusion protein.; Procedure: Biopsy/ Intratumoral Injection/ Gross Tumor Resection; On Study Day 1, the region of radiographic concern is biopsied to histologically confirm cancer recurrence versus pseudoprogression. If intraoperative pathology is consistent with cancer recurrence, then FT536 will be injected with a total volume of 1 mL infused via a ventricular catheter placed along the biopsy tract. Occurring between Study Day 8-15, the patient will undergo maximum safe surgical resection; Diagnostic test: Blood/ Cerebrospinal Fluid/ Tumor Pathology; Blood analysis will occur throughout the study to determine the quality of endogenous NK cells and T cells as well as cytokine concentrations. Cerebrospinal fluid sampling will occur at 2-3 time points throughout the study and the fluid will be analyzed for cytokines and immune cells. Compare pre- (from biopsy) versus post- (from resection) injection pathology to determine FT536 motility, replication ability, and impact on the microenvironment as well as malignant astrocytoma cell death plus the persistence of endogenous NK cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	To determine the safety and tolerability of inter-cohort dose escalation intratumoral FT536 as outlined by incidence of adverse events (AEs) based on CTCAE v5.0	1 year

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: Fate Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pathological Conditions, Signs and Symptoms; Disease Progression; Glioblastoma; Astrocytoma; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy; Blood Specimen Collection
• Other Study ID Numbers: 2024LS061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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