Retifanlimab + Bevacizumab + Radiation for Recurrent Glioblastoma

Recruiting at 2 trial locations

Overseen By Andrea McMahon

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Autoimmune diseases, Organ transplant, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: Up to 2 years

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of treatments can better manage glioblastoma, a type of brain cancer that has returned after initial improvement. The treatments include retifanlimab, an immunotherapy that aids the immune system in fighting cancer, bevacizumab (also known as Avastin), which slows tumor growth by blocking blood vessels that feed the tumor, and a special type of radiation therapy. The trial compares this combination to bevacizumab and radiation alone to determine which is more effective. This study may suit individuals whose glioblastoma has recurred, are eligible for radiation therapy, and are not currently using bevacizumab. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on certain investigational agents or treatments for autoimmune diseases, you may need to stop them before joining the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a combination of retifanlimab, bevacizumab, and a specific type of radiotherapy is safe for people with recurring glioblastoma, a type of brain cancer. Previous studies found this combination both safe and effective, with patients generally handling the treatment well.

For those receiving only bevacizumab and the radiotherapy, studies have also shown this treatment to be safe and well-tolerated. Patients experienced good results and control over their disease with this approach.

These findings suggest that both treatment options under study are safe based on earlier research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of retifanlimab with bevacizumab and radiation for recurrent glioblastoma because it offers a novel approach compared to current treatments. Unlike standard therapies that primarily focus on inhibiting blood vessel growth, retifanlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This unique mechanism of action could enhance the effectiveness of bevacizumab and radiation therapy, potentially leading to improved outcomes. Additionally, this combination might offer a synergistic effect, maximizing the potential to control tumor growth and improve survival rates.

What evidence suggests that this trial's treatments could be effective for recurrent glioblastoma?

This trial will compare two treatment combinations for recurrent glioblastoma. Arm A participants will receive a combination of retifanlimab, bevacizumab, and hypofractionated radiation therapy (HFRT). Research has shown that this combination may help treat recurrent glioblastoma, a type of brain cancer. Retifanlimab helps the immune system fight cancer cells, while bevacizumab stops tumors from growing by preventing new blood vessels from forming.

Arm B participants will receive bevacizumab and HFRT. One study found that patients who received bevacizumab and this special radiotherapy had a 50% response rate and lived for an average of 12.5 months. Using all three treatments together in Arm A could potentially lead to better results for people with recurrent glioblastoma. ^{1 3 5 6 7}

Who Is on the Research Team?

Jian L Campian

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

Adults over 18 with recurrent grade IV glioblastoma, who are candidates for radiotherapy and have a Karnofsky performance status of at least 60%. They must have adequate blood counts, organ function, and controlled steroid use. Pregnant or nursing individuals and those not using contraception are excluded. People with severe diseases or conditions that could interfere with the trial or pose risks are also ineligible.

Inclusion Criteria

Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria

I am a candidate for radiation treatment.

Absolute neutrophil count (ANC) ≥ 1,500/mm^3 (obtained ≤ 28 days prior to registration)

Exclusion Criteria

Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

I haven't taken any experimental drugs for my cancer in the last 2 weeks.

I don't have an active, severe autoimmune disease needing strong medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive retifanlimab and bevacizumab with hypofractionated radiotherapy or bevacizumab with hypofractionated radiotherapy alone. Treatment repeats every 28 days for up to 2 years.

Up to 2 years

IV administration on day 1 and 15 of each cycle, daily radiotherapy for 10 treatments starting on day 15 of cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes survival checks and adverse event monitoring.

4 years

Follow-up at 30 days post-treatment, then every 2 months for the first year, and every 6 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Hypofractionated Radiation Therapy
• Retifanlimab

Trial Overview

The trial is testing retifanlimab combined with bevacizumab and hypofractionated radiotherapy versus just bevacizumab and hypofractionated radiotherapy in treating recurrent glioblastoma. Retifanlimab is an immunotherapy drug that may help the immune system fight cancer; bevacizumab aims to stop tumor growth by inhibiting blood vessel formation.

How Is the Trial Designed?

Group I: Arm B (Bevacizumab and radiation) Experimental Treatment 6 Interventions

Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Group II: Arm A (Retifanlimab, bevacizumab and HFRT) Experimental Treatment 7 Interventions

ARM I: Patients receive retifanlimab IV over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Retifanlimab is already approved in United States for the following indications:

Approved in United States as Zynyz for:

• Merkel cell carcinoma

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a retrospective study of 14 heavily pretreated patients with recurrent high-grade gliomas, re-irradiation combined with bevacizumab showed a median progression-free survival of 5.1 months and a median overall survival of 9.0 months, indicating potential efficacy for this treatment approach.

The study found that re-irradiation with either conventional 3D-conformal or intensified modulated radiotherapy (IMRT) was feasible and generally safe, with only one case of radionecrosis detected and other side effects being typical of bevacizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas. Hundsberger, T., Brügge, D., Putora, PM., et al.[2022]

In a Phase II pilot study involving 10 patients with newly diagnosed glioblastoma, the combination of bevacizumab (BV), temozolomide (TMZ), and regional radiation therapy (RT) showed acceptable safety and tolerability, with some patients experiencing serious toxicities like presumed radiation-induced optic neuropathy and high rates of fatigue and myelotoxicity.

Preliminary results indicated encouraging mean progression-free survival, but further research with more patients and longer follow-up is needed before considering routine use of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Lai, A., Filka, E., McGibbon, B., et al.[2022]

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 study of 45 patients with glioblastoma (GBM) treated with gamma knife stereotactic radiosurgery (SRS) and bevacizumab, the combination showed promising results with a median overall survival of 13.3 months after treatment.

The treatment was found to be safe, with no radiation-related adverse events reported, and factors like Karnofsky Performance Score (KPS) and radiation dose significantly influenced progression-free survival (PFS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Knife Stereotactic Radiosurgery in Combination with Bevacizumab for Recurrent Glioblastoma. Morris, SL., Zhu, P., Rao, M., et al.[2020]

Bevacizumab, an antiangiogenic agent approved in Canada for recurrent glioblastoma, represents a significant advancement in treatment options for this aggressive brain tumor, which typically has a poor prognosis despite initial therapies.

The review discusses how bevacizumab is being used in clinical practice in Canada, along with ongoing debates regarding its effectiveness and application in glioblastoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in recurrent glioblastoma: five informative patient scenarios. Mason, WP.[2016]

In a study of 21 patients with recurrent/refractory glioblastoma treated with bevacizumab and irinotecan, the objective response rate was 33.3% and the disease-control rate was 85.7%, indicating that this combination can be an effective salvage treatment.

Factors such as a poor performance status (ECOG PS ≥3) and TP53 loss were linked to worse overall survival, while early clinical improvement after treatment was associated with better outcomes, highlighting the importance of monitoring patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors. Park, JH., Lee, HS., Choi, JW., et al.[2022]

Re-irradiation combined with bevacizumab and temozolomide is a safe and feasible treatment option for patients with bevacizumab-refractory high-grade glioma, showing a median overall survival of 8.5 months across 54 patients.

Patients who were more than 36 months from their initial radiation treatment experienced a significantly longer median overall survival of 13.3 months, suggesting that timing of re-irradiation may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas. Dixit, KS., Sachdev, S., Amidei, C., et al.[2022]

In a study of 70 patients with newly diagnosed glioblastoma, combining bevacizumab (BV) with radiation therapy (RT) and temozolomide (TMZ) resulted in improved progression-free survival (PFS) of 13.6 months compared to 7.6 months in a control group, although overall survival (OS) was similar between groups.

The presence of MGMT promoter methylation in tumor tissue was associated with better OS and PFS, suggesting that this biomarker may help identify patients who could benefit more from the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. Lai, A., Tran, A., Nghiemphu, PL., et al.[2022]

Re-irradiation is a safe treatment option for patients with recurrent glioblastoma, with only 8% experiencing severe acute toxicity, and it resulted in a median overall survival of 7.3 months and progression-free survival of 3.6 months.

Patients who had previously received bevacizumab (BEV) showed a higher rate of marginal recurrences compared to those who had not, indicating that treatment plans may need to include larger volumes of tumor abnormalities to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence. Christ, SM., Youssef, G., Tanguturi, SK., et al.[2023]

In a phase III trial involving 911 patients with newly diagnosed glioblastoma, those treated with bevacizumab had a longer safety follow-up (12.3 months) and a higher completion rate of maintenance temozolomide (64.6%) compared to placebo (36.9%).

While bevacizumab was associated with a higher incidence of adverse events such as arterial thromboembolic events (5.9% vs 1.6%) and wound-healing complications (6.9% vs 4.7%), these did not hinder patients' ability to receive standard treatment or undergo subsequent surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. Saran, F., Chinot, OL., Henriksson, R., et al.[2022]

In a study involving 25 patients with recurrent glioblastoma and anaplastic gliomas, the combination of bevacizumab and hypofractionated stereotactic radiotherapy (HFSRT) was found to be safe and well tolerated, with no cases of radiation necrosis reported.

The treatment showed promising efficacy, with a 50% overall response rate and a median overall survival of 12.5 months, indicating that this regimen could be an effective option for patients with recurrent malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Gutin, PH., Iwamoto, FM., Beal, K., et al.[2022]

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