Ignite Creation Date:
2025-12-25 @ 5:12 AM
Ignite Modification Date:
2025-12-26 @ 4:17 AM
Study NCT ID:
NCT06816927
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-06-29
First Post:
2024-12-18
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab
Sponsor:
Duke University
Organization:
Study Overview
Official Title:
A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (GIANT)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GIANT
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).
Detailed 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 chemotherapy will undergo stereotactic biopsy for histological confirmation. Cohorts of 6 patients will be accrued to receive nivolumab and relatlimab combined with RT and TMZ in the safety lead-in portion. Once determined safe, the randomized portion of the study will commence and patients will be randomized to one of two arms for neoadjuvant treatment prior to surgical resection of their tumor using an unbalanced 1:3 treatment allocation: Arm 1 - nivolumab alone or Arm 2 - nivolumab and relatlimab (combination formulation). After tumor resection, all patients will undergo Part 1 adjuvant treatment and receive RT and temozolomide (TMZ) (TMZ will be omitted in MGMT unmethylated patients), in combination with nivolumab and relatlimab. Afterwards, patients will undergo Part 2 adjuvant treatment, wherein they will receive TMZ in combination with nivolumab and relatlimab until progression or discontinuation criteria are met. All patients will be followed for 2 years after the last patients has been registered.
Primary Objectives:
1. Stage 1 - Safety Lead-In: To assess the safety of concurrently administering nivolumab, relatlimab, RT, with or without TMZ during Part 1 of the Adjuvant Treatment phase in ndGBM patients, with a specific go-no go focus on MGMT methylated patients receiving TMZ
2. Stage 2 - Randomized Phase 2: To assess the feasibility of undertaking a peri-operative study involving administration of nivolumab with or without relatlimab in patients with ndGBM
3. To establish the biological activity of nivolumab administered with or without relatlimab in patients with ndGBM, by demonstrating the presence of tumor infiltrating lymphocytes (TILs) in the resected tumor
Secondary Objectives:
1. To describe the toxicity of nivolumab administered with or without relatlimab during the neoadjuvant phase in patients with ndGBM following tumor biopsy, and prior to surgical resection of their tumor
2. To assess the safety of planned craniotomy and tumor resection performed after biopsy and neoadjuvant treatment with nivolumab administered with or without relatlimab in patients with ndGBM
3. To determine the toxicity of nivolumab administered with relatlimab during the adjuvant phase, following surgical resection of their tumor in patients with ndGBM To assess the pharmacokinetics (PK) of nivolumab administered with or without relatlimab during the neoadjuvant phase following biopsy, and prior to tumor resection for patients with ndGBM
4. To estimate the radiological response rate of nivolumab administered with or without relatlimab in ndGBM
5. To describe survival of patients who have been assigned (as in the Stage 1 safety lead-in) or randomized (Stage 2) to receive neoadjuvant nivolumab administered with or without relatlimab.
After their biopsy, patients will be randomized in the Neoadjuvant Treatment stage to receive one cycle of either nivolumab alone (Arm 1) or the combination of nivolumab and relatlimab (Arm 2). Treatment is followed by tumor resection and placement of Ommaya reservoir. After surgery, patients will enter the Part 1 Adjuvant Treatment phase and will receive RT and TMZ chemotherapy in combination with nivolumab and relatlimab. After the last dose of treatment in Part 1 Adjuvant Treatment, patients will begin the Part 2 Adjuvant Treatment phase and will receive 6 cycles of TMZ in combination with nivolumab and relatlimab. Patients that complete the treatment (i.e., complete 12 cycles of nivolumab and relatlimab with or without TMZ in the Part 2 Adjuvant Treatment Phase) or that discontinue treatment for any reason will have an End of Treatment visit and a Safety Follow-up visit 135 days after the End of Treatment visit
Patients with a ndGBM and those with a previous diagnosis of GBM who have not received prior radiation (RT), or chemotherapy will undergo stereotactic biopsy for histological confirmation. Cohorts of 6 patients will be accrued to receive nivolumab and relatlimab combined with RT and TMZ in the safety lead-in portion. Once determined safe, the randomized portion of the study will commence and patients will be randomized to one of two arms for neoadjuvant treatment prior to surgical resection of their tumor using an unbalanced 1:3 treatment allocation: Arm 1 - nivolumab alone or Arm 2 - nivolumab and relatlimab (combination formulation). After tumor resection, all patients will undergo Part 1 adjuvant treatment and receive RT and temozolomide (TMZ) (TMZ will be omitted in MGMT unmethylated patients), in combination with nivolumab and relatlimab. Afterwards, patients will undergo Part 2 adjuvant treatment, wherein they will receive TMZ in combination with nivolumab and relatlimab until progression or discontinuation criteria are met. All patients will be followed for 2 years after the last patients has been registered.
Primary Objectives:
1. Stage 1 - Safety Lead-In: To assess the safety of concurrently administering nivolumab, relatlimab, RT, with or without TMZ during Part 1 of the Adjuvant Treatment phase in ndGBM patients, with a specific go-no go focus on MGMT methylated patients receiving TMZ
2. Stage 2 - Randomized Phase 2: To assess the feasibility of undertaking a peri-operative study involving administration of nivolumab with or without relatlimab in patients with ndGBM
3. To establish the biological activity of nivolumab administered with or without relatlimab in patients with ndGBM, by demonstrating the presence of tumor infiltrating lymphocytes (TILs) in the resected tumor
Secondary Objectives:
1. To describe the toxicity of nivolumab administered with or without relatlimab during the neoadjuvant phase in patients with ndGBM following tumor biopsy, and prior to surgical resection of their tumor
2. To assess the safety of planned craniotomy and tumor resection performed after biopsy and neoadjuvant treatment with nivolumab administered with or without relatlimab in patients with ndGBM
3. To determine the toxicity of nivolumab administered with relatlimab during the adjuvant phase, following surgical resection of their tumor in patients with ndGBM To assess the pharmacokinetics (PK) of nivolumab administered with or without relatlimab during the neoadjuvant phase following biopsy, and prior to tumor resection for patients with ndGBM
4. To estimate the radiological response rate of nivolumab administered with or without relatlimab in ndGBM
5. To describe survival of patients who have been assigned (as in the Stage 1 safety lead-in) or randomized (Stage 2) to receive neoadjuvant nivolumab administered with or without relatlimab.
After their biopsy, patients will be randomized in the Neoadjuvant Treatment stage to receive one cycle of either nivolumab alone (Arm 1) or the combination of nivolumab and relatlimab (Arm 2). Treatment is followed by tumor resection and placement of Ommaya reservoir. After surgery, patients will enter the Part 1 Adjuvant Treatment phase and will receive RT and TMZ chemotherapy in combination with nivolumab and relatlimab. After the last dose of treatment in Part 1 Adjuvant Treatment, patients will begin the Part 2 Adjuvant Treatment phase and will receive 6 cycles of TMZ in combination with nivolumab and relatlimab. Patients that complete the treatment (i.e., complete 12 cycles of nivolumab and relatlimab with or without TMZ in the Part 2 Adjuvant Treatment Phase) or that discontinue treatment for any reason will have an End of Treatment visit and a Safety Follow-up visit 135 days after the End of Treatment visit
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: