Immunotherapy + Targeted Therapy + Radiation for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen ByRimas V. Lukas, MD

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Northwestern University

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults with newly diagnosed glioblastoma who have stable or decreasing steroid use, adequate blood counts and organ function, and a performance score of >=70%. They must not have had recent brain radiation or chemotherapy, certain genetic deficiencies or lung diseases, other cancers within 2 years, known allergies to the drugs tested, be pregnant/nursing, HIV/AIDS positive, drug/alcohol dependent or on immunosuppressants.

Inclusion Criteria

I am not taking any steroids as of the first day of the study.

I agree to use effective birth control during and for 5 months after the study.

I have a grade IV brain tumor with known MGMT methylation status.

I am able to care for myself but may not be able to do active work.

My kidney function, measured by creatinine levels, is within normal range.

I am able to care for myself but may not be able to do active work.

I am not taking any steroids as I start this study treatment.

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

I or my family have a history of conditions that increase the risk of methemoglobinemia.

I had a Gliadel wafer placed during my brain surgery.

I have an autoimmune disease.

I have not taken BMS-986205 or any IDO1 inhibitors before.

I have had cancer before.

I have previously received treatments targeting immune checkpoints.

I am on steroids or other drugs that affect my immune system.

I have a history of G6PD deficiency or other blood disorders.

I have or had lung inflammation treated with steroids.

I am allergic to certain cancer medications similar to nivolumab or temozolomide.

I have undergone radiation therapy for my brain.

I have a G6PD deficiency.

I am currently undergoing Optune therapy.

Participant Groups

The study tests if nivolumab (an immune system modulator), BMS-986205 (an enzyme blocker), combined with standard radiation therapy are more effective when temozolomide (a chemotherapy drug) is added. It aims to see which combination better stops tumor growth in patients with glioblastoma.

3Treatment groups

Experimental Treatment

Group I: Unmethylated Cohort (radiation, BMS-986205 50mg QD, nivolumab)Experimental Treatment3 Interventions

RADIATION 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.

Group II: Unmethylated Cohort (radiation, BMS-986205 100mg QD, nivolumab)Experimental Treatment3 Interventions

Group III: Methylated Cohort (radiation, temozolomide, BMS-986205 25mg QD, nivolumab)Experimental Treatment4 Interventions

RADIATION 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.