Giving immunotherapy before standard treatment for newly diagnosed glioblastoma

Window Studies in Glioblastoma: A Phase I Trial Investigating Neoadjuvant Ipilimumab in Newly Diagnosed Glioblastoma

This Phase 1 trial tests whether giving two doses of the immunotherapy drug ipilimumab before surgery is safe and may help people with newly diagnosed glioblastoma or gliosarcoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University College, London (Academic / other)
• Drugs / interventions: ipilimumab, immunotherapy
• Locations: 1 site (London, Greater London)
• Trial ID: NCT07134842 on ClinicalTrials.gov

What this trial studies

This is a single-center Phase 1, open-label trial of neoadjuvant ipilimumab (3 mg/kg) given up to two cycles before standard-of-care treatment, which can include debulking surgery followed by chemoradiation. The primary focus is on safety and tolerability of preoperative ipilimumab in adults with newly diagnosed supratentorial glioblastoma or gliosarcoma. Participants must be clinically fit for neoadjuvant treatment, have ECOG 0-1, and meet specified organ function criteria. The study is conducted at University College London Hospital and will monitor for immune-related effects and any impact on tumor control prior to standard therapy.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with newly diagnosed supratentorial glioblastoma or gliosarcoma, ECOG 0-1, adequate organ and bone marrow function, and judged fit for neoadjuvant therapy plus standard surgical and chemoradiation care.

Not a fit: Patients with recurrent disease, poor performance status, significant organ dysfunction, or who are not candidates for surgery or standard chemoradiation are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could help control or shrink tumor before surgery and potentially improve subsequent treatment responses.

How similar studies have performed: Small neoadjuvant immunotherapy studies in glioblastoma have shown immune changes but clear clinical benefit is unproven, and use of ipilimumab in this setting is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Radiologically or histologically confirmed, newly diagnosed de-novo supratentorial glioblastoma (including gliosarcoma)
2. Age ≥18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see appendix 3)
4. Clinically fit for, and appropriate to receive, neoadjuvant ipilimumab followed by standard of care treatment, based on investigator and MDT judgement
5. Adequate organ and bone marrow function:

   * Hb ≥9 g/dL
   * Neutrophils ≥1.5 x 109/L
   * Platelets ≥100 x 109/L
   * Lymphocyte count ≥1.0 x 109/L
6. Adequate renal function:

   • Creatinine clearance of ≥ 50mL/min calculated by Cockroft-Gault equation
7. Adequate liver function:

   * Bilirubin ≤ 1.5 x ULN (except for patients with known Gilbert's Syndrome who may have total bilirubin ≤ 3 x ULN)
   * Aspartate or alanine transferase (AST or ALT) ≤ 2.5 x ULN
8. Life expectancy of greater than 12 weeks
9. Willing to comply with the contraceptive requirements of the trial (see section 6.3.5)
10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
11. Written informed consent

Exclusion Criteria:

1. Known extracranial metastatic or leptomeningeal disease
2. Prior treatment for glioblastoma other than a biopsy or limited resection leaving residual disease
3. Dexamethasone dose \>3mg daily (or equivalent) at the time of starting study treatment
4. Antibiotics received within 30 days prior to starting study treatment, except for prophylactic antibiotics given with surgery
5. Intratumoural or peritumoural haemorrhage deemed significant by the treating clinician
6. Active autoimmune disease apart from:

   1. Skin conditions such as psoriasis, vitiligo or alopecia not requiring systemic treatment
   2. Type 1 diabetes or thyroid disease, controlled on medication
7. Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
8. Known hypersensitivity to ipilimumab or any of its excipients
9. Past medical history of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced interstitial disease which required steroid treatment or any evidence of clinically active interstitial lung disease.
10. Any condition requiring systemic treatment with corticosteroids (\>10mg prednisolone daily or equivalent) or other immunosuppressive medications within 14 days prior to starting study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10mg daily prednisolone or equivalent are permitted in the absence of active autoimmune disease.
11. Treatment with any other investigational agent within 28 days or 5 half lives of the investigational agent (whichever is longer) prior to starting ipilimumab treatment.
12. History of previous cancer within 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions
13. Positive serology for Hepatitis B defined as a positive test for HepB surface antigen (HBsAg). Note: patients who are HepB core antibody (HBcAb) positive will only be eligible for the study if the HepB virus deocyribonucleic acid (DNA) test is negative and patients are willing to undergo monthly monitoring for HBV reactivation.
14. Positive serology for Hepatitis C defined as a positive test for HCV antibody
15. Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive therapy or known HIV or acquired immunodeficiency syndrome (AIDS)-related illness
16. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
17. Women who are pregnant or breast feeding

Where this trial is running

London, Greater London

• University College London Hospital — London, Greater London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Paul Mulholland, MBBS, PhD — University College, London
• Study coordinator: WinGlio Trial Manager

Conditions Glioblastoma; Gliosarcoma, Adult; Glioblastoma - Category; phase 1; immunotherapy; Brain Cancer