Atezolizumab for Recurrent Glioblastoma

(MOAB Trial)

Recruiting at2 trial locations

Overseen by Mustafa Khasraw, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Duke University

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

Disqualifiers: Pregnancy, Autoimmune disease, Cardiovascular, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is to study if neoadjuvant atezolizumab therapy is beneficial for patients with recurrent glioblastoma and a low mutational burden.

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.

What data supports the effectiveness of the drug Atezolizumab for recurrent glioblastoma?

Atezolizumab, an immune checkpoint inhibitor, has shown clinical activity in various cancers, and a study has explored its safety and efficacy in patients with recurrent glioblastoma, suggesting potential benefits. ^{1 2 3 4 5}

Is atezolizumab safe for humans?

Atezolizumab has been studied for safety in various cancers, including glioblastoma and melanoma. While it generally shows clinical activity, it can cause immune-related side effects, such as autoimmune encephalitis (a serious brain inflammation). ^{1 3 6 7 8}

How is the drug atezolizumab unique for treating recurrent glioblastoma?

Atezolizumab is unique because it is an immune checkpoint inhibitor that targets the PD-L1 protein, helping the immune system recognize and attack cancer cells. Unlike other treatments, it leverages the body's immune response, which is particularly important for glioblastoma, a cancer with an immunosuppressive environment. ^{1 3 8 9 10}

Research Team

Mustafa Khasraw, MD

Principal Investigator

Duke University

Eligibility Criteria

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

I am 18 years old or older.

My brain tumor is confirmed as GBM without IDH mutation.

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

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

Trial Timeline

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

Treatment Details

Interventions

• Atezolizumab (Checkpoint Inhibitor)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Mary E. Klotman

Duke University

Chief Executive Officer since 2017

MD from Duke University School of Medicine

Michelle McMurry-Heath

Duke University

Chief Medical Officer since 2020

MD from Duke University School of Medicine

Findings from Research

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]

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 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]

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 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]

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 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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Nonsurgical treatment of recurrent glioblastoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Multicenter randomized controlled study of temozolomide versus semustine in the treatment of recurrent malignant glioma]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]

6. United States 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. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor. [2021]

8. United States 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study. [2020]