RecruitingPhase 2NCT06816927

Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab

A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (GIANT)

Sponsor

Duke University

Enrollment

92 participants

Start Date

Nov 28, 2025

Study Type

INTERVENTIONAL

Conditions

Newly Diagnosed Glioblastoma

Summary

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria40

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)
Life expectancy of at least 12 months
Negative human immunodeficiency virus (HIV) test at Screening
Negative hepatitis B surface antigen (HbsAg) test at Screening or positive test followed by a negative hepatitis B virus (HBV) DNA test at Screening
Negative hepatitis C antibody (anti-HCV) test at Screening or positive test followed by a negative HCV RNA test at Screening
Able to undergo brain MRI with and without contrast
People of childbearing potential must agree to use a highly effective contraceptive method (with a failure rate of \< 1%) during study treatment and for at least 6 months following the last dose of study drug and agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period. Acceptable methods of contraception are:
Combined estrogen and progestin containing hormonal contraception associated with inhibition of ovulation given orally, intravaginally, or transdermally
Progestin-only hormonal contraception associated with inhibition of ovulation given orally, by injection, or by implant
Intrauterine device: Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomised partner
Sexual abstinence: Considered a highly effective method only if defined as refraining from heterosexual intercourse during an entire period of risk associated with the study treatment. The reliability of sexual abstinence needs will be evaluated in relation to the duration of the study and to the usual lifestyle of the patient Note: People are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the person has been confirmed by follow-up hormone level assessment are they considered not of childbearing potential.
Sexually active patients that are able to produce a sperm, must use a condom during intercourse and must agree to refrain from sperm donation, from registration on the study until 3 months after the last dose of treatment
People of childbearing potential must have a negative highly sensitive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at the time of screening and within 48 hours of starting the study drug(s)
Ability to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria24

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

Interventions

DRUGNivolumab

For Neoadjuvant treatment, on both Arms 1 and 2, all 92 patients will receive single dose of 480 mg by IV infusion on Day 1 followed by surgery. Post-resection, in Part 1 Adjuvant treatment, all patients will receive two doses of 480 mg of nivolumab by IV infusion on Days 1 and 29. In Part 2 Adjuvant Treatment of Nivolumab dosing will continue for up to 12 cycles. Each cycle is 28 Days long.

DRUGRelatlimab

For Neoadjuvant treatment, only on Arm 2, 69 patients will receive a single dose of 480 mg of nivolumab and 480 mg of relatimab by IV infusions on Day 1 followed by surgery. Post resection in Part 1 Adjuvant treatment, all patients will receive two doses of 480 mg of nivolumab and relatlimab by IV infusion on Days 1 and 29. In Part 2 Adjuvant Treatment of Relatimab dosing will continue for up to 12 cycles. Each cycle is 28 Days long.

DRUGTMZ

All patients in safety lead-in, Arm 1 and Arm 2 post resection in Part 1 Adjuvant Treatment setting will receive 75 mg/m2 TMZ from Day 1 to Day 42 orally. In Part 2 Adjuvant Treatment of TMZ dosing with TMZ will continue for up to 6 cycles with 150 mg/m2 for cycle 3 and escalating to 200 mg/m2 for cycles 4 to 8 day 1 to 5 for these 6 cycles.

RADIATIONRadiation Therapy

All patients in safety lead-in, Arm 1 and Arm 2 post resection in Part 1 Adjuvant Treatment will receive External Beam Radiation 2 Gy/day (60 Gy in total) Once daily, 5 days per week, for 6 weeks Starting on Day 1

Locations(1)

Duke University

Durham, North Carolina, United States

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