Atezolizumab + Radiation for Glioblastoma

Overseen By Sumbul Yousafi, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Stony Brook University

Must not be taking: Corticosteroids, Immunosuppressive, Immunostimulatory, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat glioblastoma, an aggressive brain cancer. It combines fractionated stereotactic radiotherapy (FSRT), a targeted radiation, with Atezolizumab (Tecentriq), a drug that helps the immune system fight cancer. The goal is to determine if this combination can improve outcomes for people with newly diagnosed glioblastoma. Individuals diagnosed with glioblastoma who plan to undergo surgery to remove most of the tumor might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot continue using high-dose corticosteroids or certain immune-related treatments.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have found atezolizumab, a drug that helps the immune system fight cancer, to be safe and well-tolerated in patients with recurrent glioblastoma, a type of brain cancer. However, like other immune therapies, atezolizumab might cause the immune system to mistakenly attack healthy organs, leading to side effects.

The fractionated stereotactic radiotherapy (FSRT) used in this study is a precise type of radiation treatment. Research has shown it generally has a manageable safety profile, meaning it usually does not cause severe side effects and is considered safe when used correctly.

The combination of these treatments has been studied before, and while each has its risks, they are generally well-tolerated. Discussing potential side effects with a healthcare provider is always important to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Atezolizumab and FSRT radiation for treating glioblastoma because it represents a novel approach to tackling this aggressive brain cancer. Unlike traditional treatments like surgery, chemotherapy, and standard radiation, Atezolizumab is an immunotherapy that enhances the body's immune system to recognize and attack cancer cells. By combining it with FSRT, a more targeted form of radiation, the treatment aims to maximize tumor control while minimizing damage to surrounding healthy tissue. This innovative combination has the potential to improve outcomes by not only shrinking tumors but also by providing a more personalized attack against cancer cells.

What evidence suggests that Atezolizumab and FSRT radiation might be effective for Glioblastoma?

Research has shown that Atezolizumab, a drug that aids the immune system in fighting cancer, may effectively treat glioblastoma, a type of brain cancer. In this trial, participants will receive a combination of Atezolizumab and FSRT radiation. One study found that combining Atezolizumab with radiation was manageable for patients and performed as well as other treatments. Another study reported that patients treated with Atezolizumab lived for a median of 17.1 months. Additionally, FSRT, a type of radiation therapy that delivers precise doses to tumors, has been associated with better survival rates in glioblastoma cases. Together, these treatments might offer a new way to manage this challenging condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Alexander M. Stessin

Principal Investigator

Stony Brook Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with a new diagnosis of Glioblastoma Multiforme, a serious brain tumor. They must be candidates for surgery aiming to remove over 80% of the tumor, have good organ function and performance status (ECOG <=2), and not be pregnant. Exclusions include recent other cancers, severe infections or diseases, high steroid use, certain heart conditions, immune system issues like autoimmune disease or prior immunotherapy.

Inclusion Criteria

My organs are working well.

I can take care of myself but might not be able to do heavy physical work.

My tumor is 3.5 cm or smaller.

Exclusion Criteria

I have previously been treated with CD137 agonists or immune checkpoint inhibitors.

My cancer pain is not managed with current treatments.

My brain cancer has spread widely or affects both sides of my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fractionated stereotactic radiotherapy (FSRT) for 2 weeks, along with two doses of Atezolizumab at the beginning and end of the period

2 weeks

2 visits (in-person)

Surgery

Participants undergo craniotomy and maximal safe resection as per normal care for glioblastoma

Adjuvant Treatment

Participants follow normal care for glioblastoma in addition to Atezolizumab 840 mg IV every 2 weeks

Duration of adjuvant treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• FSRT radiation

Trial Overview The study tests Atezolizumab combined with FSRT radiation in treating Glioblastoma before and after surgical removal of the tumor. Patients will receive two doses of Atezolizumab along with two weeks of radiotherapy followed by surgery and then continue Atezolizumab every two weeks during adjuvant treatment.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 25 patients with recurrent gliomas, the combination of fractionated stereotactic radiotherapy (FSRT) and daily temozolomide (TMZ) demonstrated a median overall survival of 59 months, indicating its effectiveness as a treatment option.

The treatment was well-tolerated, with no severe side effects reported, suggesting that this approach is safe for patients undergoing re-irradiation for recurrent gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiochemotherapy with temozolomide as re-irradiation using high precision fractionated stereotactic radiotherapy (FSRT) in patients with recurrent gliomas. Combs, SE., Bischof, M., Welzel, T., et al.[2022]

In a Phase I clinical trial involving 19 patients with glioblastoma, the maximum tolerated dose of fractionated intensity-modulated radiotherapy (IMRT) combined with temozolomide (TMZ) was determined to be 65 Gy, delivered in 25 fractions over 5 weeks, without any dose-limiting toxicities observed.

The treatment was well tolerated, with only mild to moderate (Grade 1-2) neurologic and skin toxicities reported, and no severe late neurologic toxicities, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study (ISIDE-BT-1) of accelerated IMRT with temozolomide in patients with glioblastoma. Morganti, AG., Balducci, M., Salvati, M., et al.[2018]

The combination of pembrolizumab, hypofractionated stereotactic irradiation (HFSRT), and bevacizumab was found to be generally safe and well tolerated in 32 patients with recurrent high-grade gliomas, with manageable treatment-related adverse events such as proteinuria and fatigue.

In the bevacizumab-naïve group, 83% of patients showed a complete or partial response, with a median overall survival of 13.45 months, indicating promising preliminary efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. Sahebjam, S., Forsyth, PA., Tran, ND., et al.[2021]

In a study of 36 patients with recurrent glioblastoma, both stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) showed radiographic responses in some patients, with median survival times of 8.5 months for SRS and 7.4 months for FSRT, indicating both methods can be effective salvage therapies.

Patients who had a radiographic response or stable disease after treatment had significantly better survival rates (15.8 months) compared to those who did not respond (7.3 months), highlighting the importance of treatment response in predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival. Patel, M., Siddiqui, F., Jin, JY., et al.[2022]

Salvage stereotactic radiotherapy (SRT) using CyberKnife for recurrent gliomas showed an acceptable safety profile, with only 11.4% of patients experiencing significant toxicity, specifically radiation-induced brain necrosis.

The treatment resulted in a median overall survival of 9 months and a progression-free survival of 3 months, indicating that SRT can be a viable option for patients with recurrent gliomas after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife. Adachi, K., Hayashi, K., Kagawa, N., et al.[2019]

Nivolumab combined with radiotherapy and temozolomide (NIVO+RT+TMZ) is tolerable for patients with newly diagnosed glioblastoma, with no new safety concerns identified; however, higher rates of grade 3/4 treatment-related adverse events were observed compared to Nivolumab with radiotherapy alone (NIVO+RT).

The study found that overall survival (OS) was similar for patients with unmethylated MGMT promoter whether they received NIVO+RT+TMZ or NIVO+RT, indicating that the addition of temozolomide may not significantly improve outcomes in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. Omuro, A., Reardon, DA., Sampson, JH., et al.[2023]

In a phase II clinical trial involving 158 patients with newly diagnosed glioblastoma, cediranib combined with radiation and temozolomide significantly improved 6-month progression-free survival (PFS) to 46.6% compared to 24.5% for the placebo group (P = 0.005).

Although cediranib showed efficacy in prolonging PFS, it was associated with a higher incidence of grade ≥3 adverse events compared to placebo (P = 0.02), and there was no significant difference in overall survival between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NRG/RTOG 0837: Randomized, phase II, double-blind, placebo-controlled trial of chemoradiation with or without cediranib in newly diagnosed glioblastoma. Batchelor, TT., Won, M., Chakravarti, A., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor, was found to be safe and well tolerated in a phase 1a clinical trial involving 16 patients with recurrent glioblastoma, with no severe treatment-related side effects reported.

The treatment showed some efficacy, with one patient achieving a partial response and three others stabilizing their disease, while median overall survival was 4.2 months, suggesting that certain biomarkers like peripheral CD4+ T cells may help identify patients who could benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. Lukas, RV., Rodon, J., Becker, K., et al.[2020]

The combination of anti-GITR monoclonal antibody (mAb) and stereotactic radiosurgery (SRS) significantly improved survival rates in a mouse model of glioblastoma, with a cure rate of 24% compared to 0% for either treatment alone, indicating a strong immune-mediated effect.

The treatment with anti-GITR (1) and SRS led to increased infiltration of CD4+ effector T-cells and enhanced production of immune signaling molecules like IFNγ and IL-2, suggesting that this combination effectively shifts the immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. Patel, MA., Kim, JE., Theodros, D., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12034766/

Improved overall survival in an anti-PD-L1 treated cohort of ... In this study the concurrent use of atezolizumab (anti-PD-L1) with radiation and TMZ was tolerable and demonstrated efficacy in line with ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30073642/

Clinical activity and safety of atezolizumab in patients with ... The median overall survival was 4.2 months (range 1.2 to 18.8+ months). Association between peripheral CD4+ T cells and efficacy was observed.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.2511

Phase I/II study to evaluate the safety and clinical efficacy ... With median follow-up time of 16.7 months (data cutoff = 30 Dec 2019), 24 patients had died and 32 had progressed. Median OS was 17.1 months (95 ...

4. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... The treatment outcomes have remained largely unchanged in recent decades, and most GBM patients experience tumor recurrence. The unique location ...

5. braintumorcenter.ucsf.edu braintumorcenter.ucsf.edu/clinical-trial/multicenter-trial-identify-optimal-atezolizumab-biomarkers-setting-recurrent

The MOAB Trial | UCSF Brain Tumor Center In this phase II study, researchers will study whether treatment with atezolizumab provides a therapeutic benefit for patients with recurrent glioblastoma ...

6. link.springer.com link.springer.com/article/10.1007/s11060-018-2955-9

Clinical activity and safety of atezolizumab in patients with ... Atezolizumab was safe and well tolerated in this group of patients with recurrent glioblastoma. Our preliminary findings suggest that biomarkers, including ...

7. tecentriq.com tecentriq.com/safety.html

Important Safety Information | TECENTRIQ® (atezolizumab) TECENTRIQ can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work.

8. nrgoncology.org nrgoncology.org/Home/News/Post/a-safety-run-in-and-phase-ii-study-evaluating-the-efficacy-safety-and-impact-on-the-tumor-microenvironment-of-the-combination-of-tocilizumab-atezolizumab-and-fractionated-stereotactic-radiotherapy-in-recurrent-glioblastoma-nrg-bn010

A Safety Run-in and Phase II Study Evaluating the Efficacy ... The primary objective of Phase II is to determine the efficacy of the combination of tocilizumab (anti-IL6R), atezolizumab (anti-PD-L1), and FSRT in recurrent ...