92 Participants Needed

Nivolumab + Relatlimab for Glioblastoma

(GIANT Trial)

MA
MK
Overseen ByMustafa Khasraw
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients cannot be on certain treatments like immunosuppressive medications or anticoagulation therapy close to the trial start. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab + Relatlimab for Glioblastoma?

Research shows that nivolumab has been studied for glioblastoma, but with limited benefits. However, the combination of nivolumab and relatlimab has shown better results in treating melanoma, suggesting potential for improved outcomes in other cancers.12345

Is Nivolumab + Relatlimab safe for humans?

Nivolumab, used alone or with other drugs, has been generally safe in humans, but it can cause some serious side effects like liver injury and aplastic anemia (a condition where the body stops producing enough new blood cells). Nivolumab combined with Relatlimab has shown a manageable safety profile in patients with melanoma.15678

How is the drug Nivolumab + Relatlimab unique for treating glioblastoma?

Nivolumab + Relatlimab is unique because it combines two immune checkpoint inhibitors, which are designed to enhance the body's immune response against cancer cells. This approach is different from traditional treatments as it specifically targets the immune system to fight glioblastoma, a strategy that has shown promise in other types of cancer.4591011

What is the purpose of 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 is for adults with a new diagnosis of glioblastoma, which is an aggressive type of brain cancer. Participants must have a specific genetic feature in their tumor (IDH wildtype). Details on who can't join are not provided here.

Inclusion Criteria

Life expectancy of at least 12 months
Negative human immunodeficiency virus (HIV) test at Screening
Negative hepatitis B surface antigen (HbsAg) test at Screening
See 16 more

Exclusion Criteria

Abnormal troponin levels
Known allergy or sensitivity to specific medications
My tumor cannot be completely removed by surgery.
See 23 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Patients receive a single dose of nivolumab with or without relatlimab followed by tumor resection

4 weeks

Part 1 Adjuvant Treatment

Patients receive nivolumab and relatlimab with concomitant radiation and TMZ for MGMT methylated patients

6 weeks

Part 2 Adjuvant Treatment

Continuation of nivolumab and relatlimab with TMZ for up to 6 cycles

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

  • Nivolumab
  • Relatlimab
Trial Overview The GIANT study tests the combination of Nivolumab and Relatlimab immunotherapies with radiation and TMZ chemotherapy in patients with newly diagnosed glioblastoma. It's designed to see if this treatment is safe and how well it works.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Nivolumab and RelatlimabExperimental Treatment4 Interventions
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.
Group II: NivolumabExperimental Treatment3 Interventions
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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials
2,495
Recruited
5,912,000+

Findings from Research

In a study of 31 adult patients with recurrent high-grade gliomas, salvage therapy using PD-1-blocking antibodies nivolumab or pembrolizumab, with or without bevacizumab, showed a median progression-free survival of only 3.2 months, indicating limited efficacy.
The study found no significant survival benefit from these treatments in this patient population, suggesting that PD-1-blocking antibodies should be used cautiously and only in selected cases until further clinical trial results are available.
PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma.Kurz, SC., Cabrera, LP., Hastie, D., et al.[2019]
In a study of 129 patients with advanced melanoma treated with nivolumab and relatlimab, those without diabetes had significantly better progression-free survival (PFS) and overall survival (OS) compared to patients with type 2 diabetes, indicating that diabetes negatively impacts treatment efficacy.
Interestingly, patients who developed immune checkpoint inhibitor-induced diabetes (ICI-DM) during treatment had the best outcomes, suggesting that this condition may enhance the effectiveness of the therapy, possibly due to changes in LAG3 expression in tumor tissue.
The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab.Mallardo, D., Woodford, R., Menzies, AM., et al.[2023]
In a study involving 40 newly diagnosed and 86 recurrent glioblastoma patients, PD-L1 blockade with durvalumab did not meet primary efficacy endpoints, indicating it was ineffective in improving outcomes compared to standard treatments.
Recurrent glioblastoma patients exhibited significantly lower levels of circulating immune cell subsets, and the use of dexamethasone was associated with a reduction in these immune cells, suggesting that immune suppression may hinder treatment effectiveness.
Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma.Nayak, L., Standifer, N., Dietrich, J., et al.[2023]

References

Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study. [2022]
PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma. [2019]
The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab. [2023]
Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. [2023]
Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143. [2023]
Pathological characterization of nivolumab-related liver injury in a patient with glioblastoma. [2018]
Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]
Nivolumab-induced aplastic anemia: A case report and literature review. [2022]
Bilateral Optic Neuritis Secondary to Nivolumab Therapy: A Case Report. [2019]
Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
PD-1 Inhibitors: Do they have a Future in the Treatment of Glioblastoma? [2021]
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