177Lu-PSMA-617 treatment for IDH‑wildtype gliomas

LU-TARGET: A Phase 1 Study of Lutetium-177-PSMA-617 Adjuvant Radiotherapy for IDH Wild Type Gliomas Expressing PSMA Following Standard Treatment

This trial will test whether the radiopharmaceutical 177Lu-PSMA-617 is safe for adults with IDH‑wildtype gliomas who have completed standard surgery and radiation.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: bevacizumab
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT07223034 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 trial of the radioligand 177Lu-PSMA-617 in adults with histologically confirmed IDH1 R132H‑wildtype WHO grade 2–4 gliomas that show PSMA positivity by pathology. Eligible participants will undergo baseline 68Ga-PSMA PET and MRI imaging and receive one or more administrations of 177Lu-PSMA-617, with some participants also receiving temozolomide per protocol. The primary focus is dose escalation and safety monitoring, along with collection of imaging and quality-of-life data. Outcomes will determine tolerability and inform dosing for future studies of this targeted radiopharmaceutical in brain tumors.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed IDH‑wildtype WHO grade 2–4 gliomas that are PSMA-positive on pathology, who have completed standard surgery and external beam radiotherapy, have ECOG ≤2, and meet organ function and steroid-dose requirements.

Not a fit: Patients whose tumors do not express PSMA, who have IDH‑mutant gliomas, or who have poor organ function or require high-dose steroids are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If safe and tolerable, this approach could provide a new targeted radioligand therapy option for PSMA-expressing IDH‑wildtype gliomas and potentially slow tumor progression.

How similar studies have performed: 177Lu-PSMA-617 has established clinical benefit in PSMA-positive prostate cancer, but its application to glioma is novel and supported only by limited prior human data.

Eligibility criteria

Inclusion Criteria:

* Confirmed histologic diagnosis of a WHO grade 2-4 glioma that is IDH1 R132H-wildtype, including the following:

  * Diffuse astrocytoma, IDH-wildtype (grade 2-4)
  * Glioblastoma, IDH-wildtype
  * Diffuse midline glioma, H3 K27-altered
  * Diffuse hemispheric glioma, H3 G34-mutant
  * Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype PSMA positive pathological stain (by immunohistochemistry) of baseline (pre-radiotherapy) resection or biopsy sample
* Completion of standard of care therapy including surgery (for resectable tumors) and adjuvant EBRT for glioma
* Patients must be on a dose of 4 mg or less of dexamethasone (or dexamethasone equivalent steroid) for 5 days prior to first planned dose of radiopharmaceutical
* Age ≥ 18
* ECOG ≤ 2
* Serum creatinine level \< 1.5 x ULN or EGFR \> 60 mL/min
* Liver laboratory values: ALT and AST ≤ 2.5 x ULN; Albumin \> 2 g/ dL; Bilirubin \< 3 X ULN
* Normal organ and marrow function as defined as the following

  * Total white blood count \> 3.0 K/mcL
  * ANC ≥ 1.5 K/mcL
  * Platelets ≥ 100 K/mcL
  * Hemoglobin ≥ 9 g/dL
* Adequate contraception prior to registration (see section 9.0)
* Ability to understand, and willingness to sign the informed consent.

Exclusion Criteria:

* Patient known to harbor any other non-canonical IDH mutations (i.e., non-R132H)
* Target lesion within 5 mm of either the brainstem, optic chiasm or optic nerves Receipt of bevacizumab as part of the initial treatment for glioma
* Life expectancy less than 12 weeks
* Nonhealing wound, ulcer or bone fracture
* History of severe brain injury
* Patient not eligible for sequential MRI evaluations
* Patients with prior RT to \> 25% of the skeleton or prior exposure to prior Radium223, Strontium89 or Samarium153 containing compounds
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Patients with known or suspected history of grade II or higher chronic kidney disease (CKD)
* Unable to tolerate the PSMA PET/MR or PSMA PET/CT
* History of viral hepatitis or chronic liver disease with active symptoms
* History of pituitary or adrenal dysfunction
* Previously diagnosed active infection (e.g., human immunodeficiency virus \[HIV\] or viral hepatitis)
* Any condition that in the opinion of the investigator, would preclude participation in this study
* Receipt of any other investigational agents or participation in a concurrent treatment protocol
* Known allergies, hypersensitivities, or intolerance to 68Ga-PSMA-11/177Lu-PSMA-617 or its inactive compounding components
* Current or planned pregnancy
* Refusal to comply with detailed contraception requirements

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities) — Commack, New York, United States (RECRUITING)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (RECRUITING)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Brandon Imber, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Brandon Imber, MD

Conditions: Glioma, Diffuse Astrocytoma, IDH-Wildtype, Glioblastoma, IDH-wildtype, Diffuse Midline Glioma, H3 K27-Altered, Diffuse Hemispheric Glioma, H3 G34-mutant, Diffuse Pediatric-type High-grade Glioma, H3-wildtype and IDH-wildtype