An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate patients with glioblastoma that is MGMT-methylated (the MGMT gene is altered by a chemical change). Patients will receive temozolomide plus radiation therapy. They will be compared to patients receiving nivolumab in addition to temozolomide plus radiation therapy.

Official Title
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A Randomized Phase 3 Single Blind Study of Temozolomide Plus Radiation Therapy Combined With Nivolumab or Placebo in Newly Diagnosed Adult Subjects With MGMT-Methylated (Tumor O6-methylguanine DNA Methyltransferase) Glioblastoma

Conditions
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Brain Neoplasms

Intervention / Treatment
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* Drug: Nivolumab
* Drug: Temozolomide
* Radiation: Radiotherapy
* Other: Nivolumab Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Males and Females, age ≥ 18 years old Newly diagnosed brain cancer or tumor called glioblastoma or GBM Karnofsky performance status of ≥ 70 (able to take care of self) Substantial recovery from surgery resection Tumor test result shows MGMT methylated or indeterminate tumor subtype Exclusion Criteria: Biopsy-only of GBM with less than 20% of tumor removed Prior treatment for GBM (other than surgical resection) Any known tumor outside of the brain Recurrent or secondary GBM Active known or suspected autoimmune disease Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab + Temozolomide + Radiotherapy<br>Nivolumab: specified dose on specified days; IV (intravenous) infusion Temozolomide: 75 mg (milligram)/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units (joule of radiation energy per kilogram) 5 times per week for 6 weeks | Drug: Nivolumab<br> <br> * Other names: BMS-936558;Drug: Temozolomide<br> <br> * Other names: Temcad;Radiation: Radiotherapy<br> <br> * Other names: RT;|
| Placebo Comparator: Nivolumab placebo + Temozolomide + Radiotherapy<br>Nivolumab Placebo: specified dose on specified days; IV infusion Temozolomide: 75 mg/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units 5x/week x 6 weeks | Drug: Temozolomide<br> <br> * Other names: Temcad;Radiation: Radiotherapy<br> <br> * Other names: RT;Other: Nivolumab Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Determined by BICR | The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by a Blinded Independent Central Review (BICR) assessed based on Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease. | From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) | 
| Overall Survival (OS) | The time from the date of randomization to the date of death. who have not died by the end of the study will be censored to last known date alive. OS is assessed in the randomized population with no corticosteroids at baseline population and in the overall randomized population. | From randomization to date of death (up to approximately 4.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) Rates at 12 Months | Overall Survival (OS) rate is defined as the percentage of participants surviving at 12 months | From randomization to 12 months after first dose | 
| Overall Survival (OS) Rates at 24 Months | Overall Survival (OS) rate is defined as the percentage of participants surviving at 24 months | From randomization to 24 months after first dose | 
| Progression Free Survival (PFS) Based on Investigator Assessment | The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by investigator assessment based Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease. | From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) |