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

ConditionsAstrocytoma Glioblastoma Progressive Disease

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-75

SponsorMasonic Cancer Center, University of Minnesota

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

FT536
Biological/Vaccine
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.
Biopsy/ Intratumoral Injection/ Gross Tumor Resection
Procedure/Surgery
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
Blood/ Cerebrospinal Fluid/ Tumor Pathology
Diagnostic test
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

Treatment groups

9 Participants

are divided into 3 treatment groups

Group A: Dose Level Cohort -1Experimental treatment 3 interventions

Group B: Dose Level Cohort 1Experimental treatment 3 interventions

Group C: Dose Level Cohort 2Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

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

Time frame

1 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Masonic Cancer Center, University of Minnesota

Lead sponsor

Fate Therapeutics

Collaborator

Source ClinicalTrials.gov

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