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Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab

ConditionNewly Diagnosed Glioblastoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDuke University

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

Signed informed consent approved by the IRB

Adults ≥ 18 years of age

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

  • 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

Treatment groups

92 Participants
are divided into 2 treatment groups
Group A: NivolumabExperimental treatment 3 interventions
Group B: Nivolumab and RelatlimabExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
From date of registration up to 4 weeks
2

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.

Time frame
From date of registration up to 4 weeks
3

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

Time frame
From date of registration up to 2 years

Secondary outcomes

1

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

Proportion of patients who experience Grade 3+ toxicity during neoadjuvant treatment that is attributable to nivolumab and/or relatlimab utilizing CTC Ver 5.0 to assess toxicity

Time frame
From date of registration up to 2 years
2

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

30-day morbidity post biopsy or post resection

Time frame
From date of registration up to 4 weeks
3

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

Proportion of patients who experience Grade 3+ toxicity during post-surgery treatment that is attributed to nivolumab and/or relatlimab utilizing CTC Ver 5.0 to assess toxicity

Time frame
From date of registration up to 2 years
4

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

Proportion of patients within each arm with a CR or PR per RANO 2.0 criteria

Time frame
From date of registration up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Duke University

Lead sponsor

Source ClinicalTrials.gov
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