A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (GIANT)
Duke University
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).
Description
Hypotheses for GIANT: A perioperative trial of nivolumab with or without relatlimab in patients with ndGBM is feasible and safe and that we will be able to evaluate the biological effect (pharmacodynamics \[PD\]) of nivolumab monotherapy and in combination with relatlimab in this setting and determine whether there is sufficient biological activity in patients with GBM to warrant further development. Patients with a ndGBM and those with a previous diagnosis of GBM who have not received prior radiation (RT) or systemic therapy will have histological confirmation of diagnosis either by on study…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Signed informed consent approved by the IRB 2. Adults ≥ 18 years of age 3. 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 4. Patients who in the opinion of the treating neurosurgeon require resection 5. Patient is willing to undergo planned surgical procedures 6. Patient agrees to make biospecimens that will be prospectively collected (after date of consent) available for research 7. Patients who have undergone a diagnostic biopsy or…
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
Location
- Duke UniversityDurham, North Carolina