Brigimadlin + Radiation for Glioblastoma

No longer recruiting at 6 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Restricted medications

Disqualifiers: TP53 mutant, IDH mutant, others

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

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for glioblastoma, a type of brain tumor. The study aims to understand how the experimental drug Brigimadlin (also known as BI 907828) works in the body and its effects when combined with radiation therapy. It consists of two parts: one for individuals about to undergo brain tumor surgery and another for those who have already had surgery. People with a recent glioblastoma diagnosis, who are stable and not using certain medications, may be suitable candidates. Participants will visit the study site regularly for health checks and to monitor any side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take any drugs that might interfere with the trial. You can continue using corticosteroids and anti-seizure medications if they are stable or decreasing in dose, but anti-seizure medications must not interact with the trial drug, Brigimadlin.

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

Research has shown that the treatment BI 907828 (Brigimadlin) was generally safe in earlier studies, with most patients tolerating it well. In studies involving individuals with various advanced solid tumors, including biliary tract cancer, Brigimadlin demonstrated potential in fighting tumors and was safe for patients. Although some side effects occurred, they were manageable and could be controlled.

Overall, these findings suggest that Brigimadlin has been relatively safe for humans so far. However, monitoring patient responses in ongoing and future trials remains important. ^{1 2 3 4 5}

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

Most treatments for glioblastoma, such as temozolomide and bevacizumab, focus on halting tumor growth or cutting off the blood supply to cancer cells. But Brigimadlin (BI 907828) is different because it targets the MDM2-p53 interaction, a novel mechanism that could potentially reactivate the tumor-suppressing functions of p53, a protein that often gets disabled in cancer cells. This approach could effectively stop cancer cells from dividing and lead to their death, offering a fresh angle in fighting this aggressive brain cancer. Researchers are excited about Brigimadlin because it represents a promising new strategy that might enhance treatment effectiveness when combined with radiation therapy.

What evidence suggests that Brigimadlin combined with radiation therapy could be effective for glioblastoma?

Research has shown that Brigimadlin, also known as BI 907828, holds promise in treating solid tumors, including brain tumors. It blocks a protein called MDM2, which can inhibit the p53 gene from combating cancer. This action helps the p53 gene regain its natural ability to fight cancer in tumor cells with a functioning p53 gene. Studies have found Brigimadlin effective for patients with certain brain tumors, particularly those with a normal p53 gene. The treatment has demonstrated a manageable safety profile, meaning it does not cause many serious side effects. In this trial, researchers are studying Brigimadlin as a potential new treatment option for glioblastoma, an aggressive type of brain tumor. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with newly diagnosed glioblastoma, a type of brain tumor. Part 1 is for those awaiting surgery; Part 2 for post-surgery patients eligible for radiation therapy. Must be over 18, have good performance status (0 or 1), and stable health on certain medications. Excludes those with specific genetic mutations, prior systemic therapy/radiotherapy (except Phase 0 participants), poor kidney function, or incompatible implants.

Inclusion Criteria

I am a candidate for surgery to remove a brain tumor.

I had surgery to remove a brain tumor and can have standard radiotherapy.

My glioblastoma is TP53 wild type and has unmethylated MGMT promoters.

Exclusion Criteria

My grade IV astrocytoma is IDH mutant.

I have had treatment for glioblastoma, but not in a Phase 0 trial.

I cannot have an MRI due to kidney issues or metal implants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 0

Participants take a single dose of BI 907828 (Brigimadlin) as a tablet before brain surgery to assess drug uptake in the tumor

4 weeks

8 visits (in-person)

Phase 1a

Participants receive BI 907828 (Brigimadlin) in combination with standard radiation therapy to determine the highest tolerable dose

6 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 907828
• Radiation Therapy

Trial Overview The study tests BI 907828 (Brigimadlin), an MDM2 inhibitor cancer drug. Part 1 assesses how the drug accumulates in the tumor after one dose before surgery. In Part 2, the highest tolerable dose is sought alongside standard radiation therapy over six weeks with regular visits and potential continuation if beneficial.

How Is the Trial Designed?

Group I: Phase Ia Part: BI 907828 (Brigimadlin) Experimental Treatment 1 Intervention

Group II: Phase 0 Part: BI 907828 (Brigimadlin) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Intraoperative radiotherapy (IORT) for Glioblastoma results in lower exposure to organs-at-risk (OARs) compared to pre-operative single-fraction stereotactic radiosurgery (SRS), making it a safer option for patients.

The study analyzed 17 treatment plans and found that while SRS provided excellent target coverage, IORT led to significantly lower doses to critical structures like the optic nerves and retina, suggesting it may be a more effective approach in minimizing side effects during dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma. Sarria, GR., Smalec, Z., Muedder, T., et al.[2022]

A new method for delivering interstitial radiation therapy using 192Ir seeds in brain tumors has been developed, which involves CT-guided stereotactic localization and computerized dose planning.

Preliminary results from seven patients show promising outcomes with no serious complications reported, indicating the method's potential safety and efficacy in treating brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of brain tumors with iridium-192 seeds. Kaneko, I., Noguchi, M., Kogure, T., et al.[2019]

GammaTile® Surgically Targeted Radiation Therapy (STaRT) offers a novel approach to brain tumor treatment by using a bioresorbable tile that delivers radiation while minimizing direct contact with brain tissue, which helps reduce normal brain toxicity.

This therapy has been FDA approved since 2018 for recurrent brain tumors and expanded in 2020 to include newly-diagnosed malignant tumors, with ongoing trials aimed at comparing its efficacy and safety against standard radiation treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review. Odia, Y., Gutierrez, AN., Kotecha, R.[2023]

GammaTile intracranial brachytherapy, using cesium-131 seeds, was successfully performed during an awake craniotomy in a 50-year-old patient with a glioblastoma, demonstrating the safety and feasibility of this approach.

The procedure allowed for precise tumor resection and custom implantation of the GammaTiles, ensuring effective treatment while preserving critical brain functions, such as speech, due to real-time language mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of GammaTile intracranial brachytherapy implanted during awake craniotomy. McClelland, S., Gardner, UG., Le, Y., et al.[2021]

In a study of 58 patients with spinal metastases treated with intensity modulated radiation therapy using a simultaneous integrated boost (SSIB), 82% of those who reported pain before treatment experienced significant pain relief after therapy, indicating high efficacy in pain management.

The treatment demonstrated a local control rate of 88% at one year and 74% at two years, with limited acute toxicities, suggesting that SSIB is a safe and effective option for patients with spine metastases who cannot undergo stereotactic radiosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dose-Escalated Radiation Therapy With a Simultaneous Integrated Boost for the Treatment of Spinal Metastases. Florez, MA., De, B., Cavazos, A., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2017

A phase (Ph) 0/Ia study of brigimadlin concentration in ... Brigimadlin, a potent MDM2–p53 antagonist, restores wild-type (wt) p53 function and has shown early efficacy in pts with solid tumors (LoRusso ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36521007/

BI-907828, a novel potent MDM2 inhibitor, inhibits ... BI-907828 provides a promising new therapeutic option for patients with TP53 wild-type primary brain tumors.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05376800

NCT05376800 | A Study to Determine How BI 907828 ... Participants take a single dose of BI 907828 (Brigimadlin) as a tablet before the brain surgery. Part 1 of the study takes about 1 month. During this time, ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2071

PK-PD-efficacy modeling of brigimadlin in MDM2-amplified ... Brigimadlin (BI 907828) is a potent small molecule inhibitor of the p53-MDM2 pathway currently in a phase 0/1 clinical trial in combination with radiotherapy.

5. ccanewsonline.com ccanewsonline.com/issues/2024/march-2024-vol-5-no-1/efficacy-and-safety-of-brigimadlin-bi-907828-in-patients-with-advanced-btc-data-from-2-phase-1a-1b-dose-escalation-expansion-trials

Efficacy and Safety of Brigimadlin (BI 907828) in Patients ... Brigimadlin demonstrated promising preliminary activity and a manageable safety profile in patients with BTC in both phase 1a/1b trials.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.487

Efficacy and safety of brigimadlin (BI 907828), an MDM2– ... 487. Background: Outcomes remain poor for pts treated with standard-of-care chemotherapy for advanced biliary tract cancer (BTC).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37269344/

The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients ... We report phase Ia data indicating that the oral MDM2-p53 antagonist brigimadlin has a manageable safety profile and shows encouraging signs ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02696-0/fulltext

673P A phase I dose-escalation and expansion study ... BI 907828 demonstrated antitumour activity and a manageable safety profile in pts with advanced solid tumours, including those with BTC; dose expansion is ...

9. aacrjournals.org aacrjournals.org/mct/article/23/1/47/732151/Delivery-versus-Potency-in-Treating-Brain-Tumors

Delivery versus Potency in Treating Brain Tumors: BI-907828 ... Our data suggest that, despite limited BBB penetration, BI-907828 is highly efficacious in GBM pre-clinical models because to its extremely high potency in ...