Atezolizumab for Recurrent Glioblastoma

(MOAB Trial)

Recruiting at 3 trial locations

Overseen By Monika Anand, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Immunotherapy, Bevacizumab, Immunosuppressants, others

Disqualifiers: Pregnancy, Autoimmune disease, Cardiovascular, 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)

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called atezolizumab (Tecentriq) to determine its effectiveness for people with recurrent glioblastoma, a type of brain cancer, particularly those with a low mutational burden (fewer changes in their cancer cells). Researchers aim to discover if receiving atezolizumab before surgery can improve survival rates. This trial may suit individuals whose glioblastoma has returned after treatment and who are scheduled for another tumor-removal surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain immunosuppressive medications or have had recent treatments with immunotherapy or specific vaccines. It's best to discuss your current medications with the trial team.

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

Research has shown that atezolizumab is generally safe and well-tolerated for people with recurrent glioblastoma. Studies have found that patients handle the treatment without new safety issues. Common side effects in these studies were mild, such as fatigue and infusion-related reactions. This indicates that, for most people, it did not cause serious problems. While any treatment can have side effects, evidence suggests that atezolizumab is a safe option for those considering a clinical trial for recurrent glioblastoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for recurrent glioblastoma, which often include surgery, radiation, and chemotherapy, atezolizumab is a type of immunotherapy. It works by targeting and inhibiting the PD-L1 protein, which helps cancer cells evade the immune system. Researchers are excited about atezolizumab because it leverages the body's own immune system to fight the tumor, potentially offering a new way to control or reduce cancer progression. Additionally, the trial explores how tumor mutational burden (TMB) affects survival outcomes, potentially leading to more personalized treatment approaches.

What evidence suggests that atezolizumab might be an effective treatment for recurrent glioblastoma?

Research has shown that atezolizumab might help treat recurrent glioblastoma, a type of brain cancer. In earlier studies, patients who took atezolizumab, either alone or with other treatments, lived longer. Another study found that it was safe and well-tolerated by patients with this condition. Although glioblastoma is difficult to treat, these early findings suggest that atezolizumab could help some patients live longer. In this trial, all participants will receive atezolizumab, and the researchers are particularly interested in its effectiveness for patients whose tumors have fewer genetic changes. ^{2 4 5 6 7}

Who Is on the Research Team?

Mustafa Khasraw, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with recurrent glioblastoma, who've had prior radiation and TMZ treatment. They must have evidence of recurrence, tissue from their initial diagnosis, and normal levels of certain blood components like bilirubin (with exceptions for Gilbert's Syndrome), alkaline phosphatase, hemoglobin, platelets, neutrophils, and creatinine.

Inclusion Criteria

My brain tumor is confirmed as GBM without IDH mutation.

I have tissue samples from when my brain cancer was first diagnosed.

Patient or partner(s) meets criteria for non-childbearing potential or agrees to use approved methods of birth control

Exclusion Criteria

I haven't taken any immune-weakening drugs in the last 2 weeks.

I have not taken bevacizumab in the last 4 weeks.

Treatment with investigational therapy within 28 days prior to initiation of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgery Treatment

Participants receive one dose of atezolizumab prior to surgical debulking

1 week

1 visit (in-person)

Post-Surgery Treatment

Participants receive post-operative atezolizumab until progression, unacceptable toxicity, death, or withdrawal of consent

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab

Trial Overview The MOAB Trial is testing whether Atezolizumab given before surgery can help patients with recurrent glioblastoma that has a low number of genetic mutations. The study aims to find the best biomarkers to predict the effectiveness of this therapy.

How Is the Trial Designed?

Group I: Pre-Surgery Atezolizumab Experimental Treatment 1 Intervention

80 patients with rGBM who are eligible for surgical debulking will be treated with one dose of atezolizumab prior to resection. Resected tissue will be used to pathologically confirm recurrence, and tumor tissue will be analyzed by whole exome sequencing (WES). Anticipating that40 patients with low TMB and 40 with high TMB will be treated. All treated subjects will receive post-operative atezolizumab until progression, unacceptable toxicity, death or withdrawal of consent. Post-atezolizumab survival will be compared between low vs high TMB arms to determine if low TMB associates with longer survival after atezolizumab

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?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

In a study of 151 patients with recurrent glioblastoma multiforme or anaplastic astrocytoma, temozolomide (TMZ) demonstrated significantly better progression-free survival (78.87%) compared to semustine (Me-CCNU) (55.88%), indicating its superior efficacy.

TMZ also had a lower rate of adverse events (29.11%) compared to Me-CCNU (45.15%), suggesting that TMZ is not only more effective but also has a better safety profile for treating these types of brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Multicenter randomized controlled study of temozolomide versus semustine in the treatment of recurrent malignant glioma]. Sun, J., Yang, XJ., Yang, SY.[2018]

In a study of 21 patients with recurrent glioblastoma, the combination of anlotinib and temozolomide resulted in a high objective response rate of 81% and a median progression-free survival of 7.3 months, indicating significant efficacy in managing this aggressive cancer.

The treatment was generally well-tolerated, with the most common side effects being leukocytopenia and thrombocytopenia, and no treatment-related deaths were reported, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma. Xu, Q., Huang, K., Meng, X., 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]

In a study of 290 patients treated with atezolizumab, 7 developed autoimmune encephalitis, with 5 patients analyzed, revealing that 60% of those affected shared the rare HLA-B*27:05 genotype, which is significantly more common in this group than in the general population.

The strong association between the HLA-B*27:05 genotype and atezolizumab-induced encephalitis (odds ratio of 59) suggests that HLA screening could be valuable in identifying patients at risk for this serious immune-related adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor. Chang, H., Shin, YW., Keam, B., et al.[2021]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

In a study of 31 patients with recurrent glioblastoma treated with apatinib and temozolomide, the combination showed an objective response rate of 26.3% and a disease control rate of 84.2%, indicating it can be an effective treatment option.

The treatment resulted in a median progression-free survival of 4.9 months and overall survival of 8.2 months, with manageable side effects such as hypertension and decreased appetite, suggesting it is a viable salvage therapy for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma. Ge, J., Li, C., Xue, F., et al.[2022]

Standard treatment for glioblastoma multiforme includes surgery, radiotherapy, and chemotherapy with temozolomide, but nearly all patients experience disease recurrence, complicating further treatment options.

Currently, there is no established standard for second-line treatment after recurrence, with various options like antiangiogenics and EGFR inhibitors being explored, but the effectiveness of these treatments remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsurgical treatment of recurrent glioblastoma. Gallego, O.[2023]

In a phase II study involving 80 patients with recurrent glioblastoma, pembrolizumab combined with bevacizumab showed a 6-month progression-free survival (PFS-6) of 26% and a median overall survival (OS) of 8.8 months, indicating limited efficacy despite being well tolerated.

Pembrolizumab alone had a much lower PFS-6 of 6.7% and no objective responses, suggesting that while the combination therapy had some durable responses, neither treatment was effective enough for significant clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Nayak, L., Molinaro, AM., Peters, K., et al.[2022]

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

In a study of 30 patients with recurrent disseminated glioblastoma, the combination of recombinant human endostatin (rh-ES) with temozolomide and irinotecan resulted in a 6-month progression-free survival rate of 23.3% and a median overall survival of 6.9 months, indicating its potential efficacy as a treatment option.

The treatment was associated with manageable adverse effects, primarily hematologic toxicities and gastrointestinal issues, suggesting that while side effects occurred, they were not severe enough to outweigh the benefits of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study. Ge, JJ., Li, C., Qi, SP., et al.[2020]

Citations

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

Clinical activity and safety of atezolizumab in patients with ... Conclusions: Atezolizumab was safe and well tolerated in this group of patients with recurrent glioblastoma. Our preliminary findings suggest ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06069726

Study Details | NCT06069726 | A Multicenter Trial to ... This is to study if neoadjuvant atezolizumab therapy is beneficial for patients with recurrent glioblastoma and a low mutational burden. Detailed Description.

3. nature.com nature.com/articles/s41467-025-56930-7

Improved overall survival in an anti-PD-L1 treated cohort of ... This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab ...

4. 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 ...

5. withpower.com withpower.com/trial/atezolizumab-for-recurrent-glioblastoma-e2c83

Atezolizumab for Recurrent Glioblastoma (MOAB Trial) In a study of 21 patients with recurrent glioblastoma, the combination of anlotinib and temozolomide resulted in a high objective response rate of 81% and a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10639569/

CTIM-23. SAFETY RUN-IN RESULTS OF A PHASE I/II ... The combination of atezolizumab with cabozantinib was tolerable, and no new safety signals were noted. In this small cohort of recurrent GBM patients, ...

7. 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 ...