Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab

NCT06816927 | Recruiting Phase 2 FDA Drug

• 1 other identifier: Pro00116940
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Newly Diagnosed Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Assess the safety of concomitantly administering nivolumab, relatlimab, RT, and TMZ in MGMT methylated patients by monitoring adverse events utilizing CTC Version 5.0 criteria

  Proportion of patients with MGMT methylation who experience an unacceptable toxicity during concomitant nivolumab, relatlimab, RT and TMZ by assessing adverse events reported utilizing CTC Version 5.0 criteria

  From date of registration up to 4 weeks

• Assess the feasibility of undertaking a peri-operative study of nivolumab with or without relatlimab in patients with ndGBM (Newly diagnosed Glioblastoma)

  Proportion of registered patients who undergo biopsy, receive one cycle of randomized neoadjuvant immunotherapy, and undergo surgery during the neoadjuvant phase of the study, OR undergo biopsy that documents the patient to not have GBM. Proportion of randomized patients who receive one cycle of randomized neoadjuvant immunotherapy, and undergo surgery.

  From date of registration up to 4 weeks

• Establish the biological activity of nivolumab with or without relatlimab in patients with ndGBM by demonstrating the presence of Tumor-infiltrating lymphocytes (TILs) in the resected tumor

  Changes in TILs in formalin-fixed paraffin embedded (FFPE) tumor sections from biopsy to resection during concomitant nivolumab, relatlimab, RT and TMZ

  From date of registration up to 2 years

Secondary Outcomes (8)

• Describe the toxicity of nivolumab with or without relatlimab in patients with ndGBM following biopsy, and prior to surgery

  From date of registration up to 2 years

• Assess the safety of planned craniotomy and resection after stereotactic biopsy and treatment with nivolumab with or without relatlimab in patients with ndGBM

  From date of registration up to 4 weeks

• Assess the safety of nivolumab and relatlimab in combination with standard of care chemoradiation in patients with ndGBM.

  From date of registration up to 2 years

• Determine the radiological response to nivolumab with or without relatlimab in ndGBM

  From date of registration up to 2 years

• Describe Overall Survival (OS) and Progression Free Survival (PFS) of patients who have been randomized or assigned (as in the Stage 1 safety lead-in) or randomized (Stage 2) to receive neoadjuvant nivolumab administered with or without relatlimab

  From date of registration up to 2 years

Study Arms (2)

Nivolumab

EXPERIMENTAL

4 stages of treatment on Arm 1 are: 1. Neoadjuvant Treatment: Patient will receive a single dose of 480 mg by IV infusion on Day 1. 2. Resection 3. Part 1 Adjuvant Treatment: Patient will receive 480 mg of nivolumab and 380 mg of relatimab for up to 12 cycles with concomitant radiation 2Gy/day (60 Gy in total). All MGMT methylated patients under Part 1 Adjuvant Treatment setting will also receive 75 mg/m2 TMZ from Day 1 to Day 42 orally. 4. Part 2 Adjuvant Treatment: Part 1 Adjuvant Treatment will continue without concomitant radiation.

Drug: Nivolumab; Drug: TMZ; Radiation: Radiation Therapy

Nivolumab and Relatlimab

EXPERIMENTAL

In Arm 2 and Safety Lead-In phase, patients will receive treatment in 4 stages as below: 1. Neoadjuvant Treatment: Patient will receive a single dose of 480 mg by IV infusion with 480 mg of relatimab on Day 1. 2. Resection 3. Part 1 Adjuvant Treatment: Patient will receive 480 mg of nivolumab and 480 mg of relatimab for up to 12 cycles with concomitant radiation 2Gy/day (60 Gy in total). All MGMT methylated patients under Part 1 Adjuvant Treatment setting will also receive 75 mg/m2 TMZ from Day 1 to Day 42 orally. 4. Part 2 Adjuvant Treatment: Part 1 Adjuvant Treatment will continue without concomitant radiation.

Drug: Nivolumab; Drug: Relatlimab; Drug: TMZ; Radiation: Radiation Therapy

Interventions

Relatlimab DRUG

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.

Nivolumab and Relatlimab

TMZ DRUG

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.

Nivolumab; Nivolumab and Relatlimab

Radiation Therapy RADIATION

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

Nivolumab; Nivolumab and Relatlimab

Nivolumab DRUG

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.

Nivolumab; Nivolumab and Relatlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27750, United States

RECRUITING

Related Publications (1)

• Long GV, Shklovskaya E, Satgunaseelan L, Mao Y, da Silva IP, Perry KA, Diefenbach RJ, Gide TN, Shivalingam B, Buckland ME, Gonzalez M, Caixeiro N, Vergara IA, Bai X, Rawson RV, Hsiao E, Palendira U, Phan TG, Menzies AM, Carlino MS, Quek C, Grimmond SM, Vissers JHA, Yeo D, Rasko JEJ, Khasraw M, Neyns B, Reardon DA, Ashley DM, Wheeler H, Back M, Scolyer RA, Drummond J, Wilmott JS, Rizos H. Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma. Nat Med. 2025 May;31(5):1557-1566. doi: 10.1038/s41591-025-03512-1. Epub 2025 Feb 27.

  PMID: 40016450 DERIVED

MeSH Terms

Interventions

Nivolumab; relatlimab; Radiotherapy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Central Study Contacts

Mustafa Khasraw

CONTACT

9196845301; mustafa.khasraw@duke.edu

Monika Anand

CONTACT

7326818838; monika.anand@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery • Neuro Oncology

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: February 10, 2025
• Study Start: November 28, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2031
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)