FT536 injection for recurrent WHO Grade 4 astrocytoma

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

This will try a single intratumoral dose of FT536, an off-the-shelf engineered NK‑cell therapy, in adults undergoing repeat surgery for recurrent Grade 4 astrocytoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Masonic Cancer Center, University of Minnesota (Academic / other)
• Drugs / interventions: bevacizumab, radiation, chimeric antigen receptor, immunotherapy
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT07560865 on ClinicalTrials.gov

What this trial studies

This single-center, first-in-cancer-type Phase I trial administers one intratumoral injection of FT536 at the time of biopsy in adults with first or second recurrence of WHO Grade 4 astrocytoma, followed 7–14 days later by maximum safe gross tumor resection. FT536 is an allogeneic NK-cell product derived from an iPSC line engineered with CD38 knockout, a MICA/B CAR, a high-affinity non‑cleavable CD16 receptor, and an IL‑15/IL‑15Rα fusion to boost activity and persistence. Patients are eligible regardless of IDH status if gross total resection is feasible and they meet performance and organ function criteria. The study focuses on safety, feasibility, and local biological activity of the intratumoral infusion surrounding standard surgical care.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed recurrent WHO Grade 4 astrocytoma (first or second recurrence), a Karnofsky performance status ≥70, and for whom gross tumor resection is deemed feasible are ideal candidates.

Not a fit: Patients who cannot undergo repeat craniotomy, have poor performance status, widespread unresectable disease, or active uncontrolled medical issues are unlikely to benefit from this localized therapy.

Why it matters

Potential benefit: If successful, this approach could enhance local anti-tumor immune activity after surgery and potentially improve tumor control and clinical outcomes for some patients.

How similar studies have performed: Engineered NK‑cell therapies have shown encouraging early results in hematologic cancers, but use of CAR or iPSC-derived NK cells intratumorally in high‑grade gliomas is largely novel and unproven.

Eligibility criteria

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

Where this trial is running

Minneapolis, Minnesota

• Elizabeth C. Neil, MD — Minneapolis, Minnesota, United States (Recruiting)

Conditions Astrocytoma; Glioblastoma; Progressive Disease