Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab

Recruiting now · Phase 2

Conditions studied: Newly Diagnosed Glioblastoma

In brief

GIANT is an open-label, multi-center, randomized, perioperative (neoadjuvant followed by adjuvant), phase 2 trial with a safety lead-in phase to investigate the feasibility, safety and tolerability, and establish the biological activity of nivolumab with or without relatlimab in patients with isocitrate dehydrogenase (IDH) wildtype newly diagnosed glioblastoma (ndGBM).

Key facts

Study ID

NCT06816927

Run by

Duke University

People needed

92

Starts

2025-11-28

Expected to finish

2031-06-01

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed informed consent approved by the IRB
• Adults ≥ 18 years of age
• Patients with either:
• A newly suspected diagnosis of GBM based on MRI
• A previous diagnosis of GBM and who have not received prior RT or systemic therapy for their brain tumor
• Patients who in the opinion of the treating neurosurgeon require resection
• Patient is willing to undergo planned surgical procedures
• Patient agrees to make biospecimens that will be prospectively collected (after date of consent) available for research
• Patients who have undergone a diagnostic biopsy or open surgical procedure prior to enrolling in this study:
• If adequate archival tissue, defined as at least 3 blocks, is readily available, there is clear documentation of its availability, and the patient must consents to provide that tissue, the patient does not need to undergo another biopsy prior to, or on study, in order to be eligible for this trial
• If archival tissue is sufficient as described above, patient must have either residual enhancing disease requiring resection, or molecularly confirmed GBM with a clear clinical indication for additional resection, as determined by the country PI (or delegate) and the designated trial surgeon.
• If archival tissue is insufficient, or if the patient previously underwent a needle biopsy and there is no clear documentation of tissue availability, and the patient wishes to enroll, the patient must agree to undergo a repeat biopsy as part of this study prior to Screening.
• Hematological function as follows:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Haemoglobin > 90 g/L
• Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.5 x upper limit of normal (ULN)
• Renal function as follows:
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula (Appendix 1)
• Hepatic function as follows:
• Total bilirubin ≤ 1.5 x ULN (Exception: Patient has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable)
• Alkaline phosphatase (ALP) ≤ 2.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Serum albumin ≥ 25 g/L
• Eastern Co-operative Oncology Group (ECOG) performance status of 0-1 (Appendix 2)

You may not qualify if…

• Tumors where a gross total resection is not considered feasible by the treating neurosurgeon
• Tumor involves cerebellum, brainstem, or deep basal ganglia
• Patients who require urgent resection for mass effect, cerebral edema, or hydrocephalus in the opinion of the treating neurosurgeon
• Patients with contraindications to MRI or unwilling to undergo MRI
• History of CNS bleeding as defined by stroke within 6 months prior to registration
• Contraindication to surgery
• Treatment with immunosuppressive medications Note: Low-dose corticosteroids (≤ 2 mg/day dexamethasone or equivalent) for tumor-associated edema is permitted. Patients who require corticosteroids > 2mg/day dexamethasone (or equivalent) for acute emergencies during the screening window will be eligible, if the corticosteroid dosing reduces to ≤ 2 mg/day dexamethasone (or equivalent) at least one day prior to the initial trial-mandated biopsy.
• Active autoimmune disease or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
• Active tuberculosis
• Patient has had a previous SARS-CoV-2 infection either suspected or confirmed within 4 weeks prior to screening. Acute symptoms must have resolved and based on treating physician's assessment, there are no sequelae that would place the patient at a higher risk of receiving trial treatment
• Evidence of acute intracranial/intra-tumoral hemorrhage, which requires urgent intervention
• Severe infection within 4 weeks prior to registration
• Treatment with a live, attenuated vaccine within 4 weeks prior to registration, or anticipation of need for such a vaccine during study or within 5 months after final dose of nivolumab and relatlimab
• Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin or other malignancies with no evidence of disease for 2 years or more
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to registration
• History of idiopathic pulmonary fibrosis, organising pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Patient is pregnant or breastfeeding/chestfeeding
• Prior allogeneic stem cell or solid organ transplantation
• Known allergy or sensitivity nivolumab, relatlimab, temozolomide or their excipients
• Patient has any kind of disorder that, in the opinion of the site PI, may compromise the ability of the patient to give written informed consent and/or to comply with all required study procedures
• Patients with a history of myocarditis
• Patient has troponin T (TnT) or I (TnI) > 2 × ULN Note: Patients with TnT or TnI levels between > 1 × to 2 × ULN will be eligible if repeat levels within 24 hours are ≤ 1 × ULN. If TnT or TnI levels are between > 1 × to 2 × ULN within 24 hours, the patient must be evaluated by a cardiologist. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 × ULN, the patient must be evaluated by a cardiologist. After cardiologist evaluation, the patient may be eligible if the site PI assesses a favorable benefit/risk
• Left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 6 months prior to registration
• History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the site PI would pose a risk to patient safety or interfere with the study evaluation, procedures or completion

Where it is running

• Duke University — Durham, North Carolina, United States (enrolling)
• Peter MacCallum Cancer Centre — Parkville, Victoria, Australia (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.