Nivolumab, BMS-986205, and Radiation Therapy With or Without Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma
Combination of Checkpoint Inhibition and IDO1 Inhibition Together With Standard Radiotherapy or Chemoradiotherapy in Newly Diagnosed Glioblastoma. A Phase 1 Clinical and Translational Trial
5 other identifiers
interventional
18
1 country
1
Brief Summary
This phase I trial studies the side effects of nivolumab, BMS-986205, and standard radiation therapy with or without temozolomide in treating patients with new diagnosed glioblastoma. Immunotherapy with nivolumab, may induce changes in body?s immune system and may interfere with the ability of tumor cells to grow and spread. BMS-986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and BMS-986205 may work better compared to radiation therapy and temozolomide alone in treating patients with newly diagnosed glioblastoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2019
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 5, 2019
CompletedFirst Posted
Study publicly available on registry
August 7, 2019
CompletedStudy Start
First participant enrolled
August 13, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
June 29, 2025
June 1, 2025
7.5 years
August 5, 2019
June 25, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events (AEs)
Drug safety and tolerability will be evaluated by descriptively summarizing AEs, laboratory assessments, vital signs, and electrocardiogram assessments using tables of frequencies and counts for categorical variables and means (sds) or medians (ranges, interquartile ranges) for continuous variables.
Up to 30 days after last dose
Secondary Outcomes (7)
Overall survival
Up to 1 year
Median survival
Up to 1 year
Progression free survival at 6 months
Up to 6 months
Median time to disease progression
Up to 1 year
Radiographic response rates (RR)
Up to 3 years
- +2 more secondary outcomes
Study Arms (3)
Methylated Cohort (radiation, temozolomide, BMS-986205 25mg QD, nivolumab)
EXPERIMENTALRADIATION THERAPY: Patients with MGMT methylated promoter undergo radiation therapy 5 days per week (Monday-Friday) for up to 6 weeks. Patients also receive temozolomide PO QD, IDO1 inhibitor BMS-986205 PO QD, and nivolumab IV over 30 minutes every 2 weeks for up to 6 weeks in the absence of disease progression, unacceptable toxicity, withdrawal of consent, the study ends, or until Q4W dosing begins. MAINTENANCE THERAPY: Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-5 and on day 1 of subsequent cycles. Within 4 weeks of radiation therapy completion, patients also receive temozolomide PO QD on days 1-5 of cycles 2-6. Cycles repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Unmethylated Cohort (radiation, BMS-986205 50mg QD, nivolumab)
EXPERIMENTALRADIATION THERAPY: Patients with MGMT unmethylated promoter undergo radiation therapy 5 days per week (Monday-Friday) for up to 6 weeks. Patients also receive IDO1 inhibitor BMS-986205 PO QD and nivolumab IV over 30 minutes every 2 weeks for up to 6 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-5 and on day 1 of subsequent cycles. Cycles repeats every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity, withdrawal of consent, the study ends, or until Q4W dosing begins.
Unmethylated Cohort (radiation, BMS-986205 100mg QD, nivolumab)
EXPERIMENTALRADIATION THERAPY: Patients with MGMT unmethylated promoter undergo radiation therapy 5 days per week (Monday-Friday) for up to 6 weeks. Patients also receive IDO1 inhibitor BMS-986205 PO QD and nivolumab IV over 30 minutes every 2 weeks for up to 6 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive IDO1 inhibitor BMS-986205 PO QD on days 1-28 and nivolumab IV over 30 minutes on days 1 and 15 of cycles 1-5 and on day 1 of subsequent cycles. Cycles repeats every 28 days for up to 2 years in the absence of disease progression, unacceptable toxicity, withdrawal of consent, the study ends, or until Q4W dosing begins.
Interventions
Given PO
Given IV
Undergo radiation therapy
Given PO
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have a newly diagnosed histologically confirmed diagnosis of any grade IV glioma with documentation of MGMT methylation status. The histological diagnosis can be obtained either from a brain biopsy or from a neurosurgical resection of the tumor
- Note: Study enrollment is to be within 5 weeks from diagnostic surgery or biopsy
- Note: Pyrosequencing to determine MGMT methylation status will be performed at Northwestern Memorial Hospital as standard of care (SOC)
- Tumor tissue specimens from the GBM surgery or biopsy for central pathology review and exploratory analysis of immunocorrelative studies, if available (no minimum requirement)
- For subjects who had undergone tumor resection, preoperative gadolinium (Gd)-magnetic resonance imaging (MRI) and immediate postoperative Gd-MRI performed within \< 72 hours after surgery or biopsy is recommended. If computed tomography (CT) scans were performed perioperatively, an MRI should be performed before initiation of study treatment
- Patients must exhibit a Karnofsky performance score of \>= 70%
- Stable or decreasing dose of steroids for \>= 7 days prior to registration
- Note: Patients must be off of all steroids at the time of initiation of study treatment (day 1 \[D#1\])
- Patients must have adequate organ and bone marrow function at registration, as defined below:
- Absolute neutrophil count \>= 1500/mm\^3
- Platelets \>= 100,000/mm\^3
- Creatinine or creatinine clearance =\<1.5 times upper limit of normal or \>= 60 mL/min
- Hemoglobin \>=10 mg/dL
- Blood transfusion allowed
- Total bilirubin =\< 1.5 times upper limit of normal
- +10 more criteria
You may not qualify if:
- Patients who have had chemotherapy within 2 years prior to entering the study are not eligible
- Patients who have received brain radiation therapy (RT) are not eligible
- Patients may not be receiving any other investigational agents. Patients may not have received an investigational agent within the past 30 days prior to the initiation of study treatment
- Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications are not eligible
- Note: Inhaled or topical steroids, and adrenal replacement steroid doses \>= 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Patients with an active, known or suspected autoimmune disease are not eligible. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- Participants with a personal or family (i.e., in a first-degree relative) history or presence of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that puts them at risk of methemoglobinemia are not eligible. All participants will be screened for methemoglobin levels prior to registration
- Participants with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders are not eligible. All participants will be screened for G6PD levels prior to registration
- Participants with active interstitial lung disease (ILD)/pneumonitis or with a history of ILD/pneumonitis requiring steroids are not eligible
- Patients with a history of recent prior malignancy are not eligible. Subjects with curatively treated cervical carcinoma in situ or non-melanoma basal cell carcinoma of the skin, or subjects who have been free of other malignancies for \>= 2 years are eligible for this study
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, temozolomide or BMS-986205 are not eligible
- Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways are not eligible
- Patients who have had prior treatment with BMS-986205 or any other IDO1 inhibitors are not eligible
- Patients who have received treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 14 days prior to registration are not eligible
- Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Northwestern University
Chicago, Illinois, 60611, United States
Related Publications (1)
Wainwright D, Lukas R, Zhai L, Lauing K, Kim M, Koch T, Penco-Campillo M, Bommi P, Dixit K, Kumthekar P, Sharp L, Lezon R, Garcia D, Sonabend A, McCortney K, Castro B, Chandler J, Gondi V, Grimm S, Heimberger A, Dobinda K, Zhang H, Sachdev S, Juhasz C, James CD, Allen J, Horbinski C, Lesniak M, Stupp R, Miska J. Newly diagnosed glioblastoma IDHwt patients treated with radiation, nivolumab, and BMS-986205. Res Sq [Preprint]. 2025 Sep 25:rs.3.rs-7567487. doi: 10.21203/rs.3.rs-7567487/v1.
PMID: 41041559DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rimas V Lukas, MD
Northwestern University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 5, 2019
First Posted
August 7, 2019
Study Start
August 13, 2019
Primary Completion (Estimated)
February 15, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
June 29, 2025
Record last verified: 2025-06