Brigimadlin for Liposarcoma

Not currently recruiting at 82 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: MDM2-p53 antagonists

Disqualifiers: TP53 mutation, Major surgery, Brain metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 23 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called brigimadlin for individuals with dedifferentiated liposarcoma (DDLPS). Researchers aim to determine if brigimadlin, designed to target and inhibit the protein MDM2, can effectively help and be tolerated by those with this cancer. Participants will take a brigimadlin tablet every three weeks and undergo regular check-ups to monitor health and tumor size. Eligible participants must have DDLPS with specific MDM2 characteristics. This trial may suit those who haven't responded to or have not yet tried other DDLPS treatments. As a Phase 3 trial, it represents the final step before potential FDA approval, offering participants a chance to contribute to a promising treatment's journey to becoming widely available.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that you cannot take any drugs that might interfere with the study. It's best to discuss your current medications with the study doctors to see if they are allowed.

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

Research has shown that brigimadlin, the treatment under study, is generally safe. In earlier studies, brigimadlin was tested on patients with various types of cancer, including bile duct cancer and dedifferentiated liposarcoma (DDLPS). Many patients tolerated the treatment well and experienced positive results. Some patients did encounter side effects, but doctors found these were usually manageable.

Thus, brigimadlin is generally well-tolerated. However, like any cancer treatment, healthcare professionals must monitor patients to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for liposarcoma, like surgery and chemotherapy, focus on removing or shrinking the tumor. But Brigimadlin works differently, targeting a protein called MDM2, which is involved in cancer cell growth. Researchers are excited about Brigimadlin because it has the potential to stop tumor growth by neutralizing this protein, which isn't the focus of traditional treatments. This new mechanism of action could lead to more effective management of liposarcoma, offering hope for better outcomes.

What evidence suggests that brigimadlin might be an effective treatment for liposarcoma?

Research has shown that brigimadlin, the treatment under study in this trial, may help treat dedifferentiated liposarcoma (DDLPS), a type of cancer. In one study, 11.1% of patients responded well to brigimadlin, and 74.1% experienced their cancer stopping or shrinking. This treatment blocks MDM2, a protein that aids cancer growth, potentially slowing or stopping tumor growth. Patients with DDLPS who took brigimadlin showed positive results with manageable side effects. While more research is needed, these early findings are promising. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with a specific cancer called dedifferentiated liposarcoma (DDLPS) that tests positive for MDM2 can join this study. They must not have had prior systemic therapy for DDLPS, be able to use effective birth control, and have a life expectancy of at least 3 months. Participants need to be in fairly good health (ECOG status of 0 or 1) and over the age of 18.

Inclusion Criteria

I have at least one tumor that can be measured for treatment response.

You must provide a signed and dated written consent form compliant with ICH-GCP guidelines and local laws prior to participating in any study activities.

WOCBP and men able to father a child must be willing and equipped to utilize two medically sound forms of contraception per ICH M3 (R2) that have an exceedingly low amount of failure when used accurately and continually from screening, throughout the study duration, until 6 months and 12 days after last dose for women or 102 days after last dose for men

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take brigimadlin as a tablet once every 3 weeks. They continue as long as they benefit and can tolerate it. Regular health checks and tumour size assessments are conducted.

up to 23 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brigimadlin

Trial Overview The trial is testing Brigimadlin, an MDM2 inhibitor cancer drug. Patients will take it as a tablet every three weeks and continue if they benefit without severe side effects. Their health, tumour size, and any unwanted effects are checked regularly by doctors at the study site.

How Is the Trial Designed?

Group I: Brigimadlin treatment 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

The study of RG7112, an MDM2 antagonist, in 20 patients with MDM2-amplified liposarcoma showed significant activation of the P53 pathway, with P53 and P21 levels increasing by 4.86 and 3.48 times, respectively, after 8 days of treatment.

While RG7112 demonstrated the ability to inhibit tumor cell proliferation, resulting in one partial response and 14 cases of stable disease, it also caused adverse effects in all patients, with common issues including nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Ray-Coquard, I., Blay, JY., Italiano, A., et al.[2022]

In a phase II study involving 270 patients with advanced liposarcoma or leiomyosarcoma, the trabectedin regimen administered every 3 weeks via a 24-hour infusion showed a significantly longer median time to progression (3.7 months) compared to the weekly 3-hour infusion regimen (2.3 months).

The 3-week regimen also demonstrated better progression-free survival (3.3 months vs. 2.3 months) and was generally well tolerated, with rare occurrences of severe side effects like febrile neutropenia, suggesting trabectedin is a promising treatment option for patients who have not responded to standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. Demetri, GD., Chawla, SP., von Mehren, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10401071/

The MDM2–p53 Antagonist Brigimadlin (BI 907828) in ... Preliminary efficacy was encouraging (11.1% overall response and 74.1% disease control rates), particularly in patients with well-differentiated or ...

2. esmoopen.com esmoopen.com/article/S2059-7029(24)00214-X/fulltext

56O A phase Ia/Ib study of the MDM2-p53 antagonist ... Brigimadlin q3w demonstrated manageable toxicity and encouraging efficacy with a high rate of disease control in DDLPS pts. Brigimadlin is being evaluated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06058793

NCT06058793 | Brightline-4: A Study to Test How Well ... This study is open to adults with a type of cancer called dedifferentiated liposarcoma (DDLPS). They can join the study if their tumours are positive for ...

4. dailyreporter.esmo.org dailyreporter.esmo.org/esmo-sarcoma-and-rare-cancers-congress-2024/highlights/new-hope-for-mdm2-inhibition-in-liposarcomas

New hope for MDM2 inhibition in liposarcomas? Early-phase trial shows efficacy of brigimadlin in liposarcomas, but confirmation from phase III results is still awaited.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150605/

Real-world survival outcomes and MDM2 prevalence in US ... This real-world study highlights the need for better systemic therapies, as median OS was 12.6 months (95% CI: 8.6–19.8) for the overall metastatic DDLPS cohort ...

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

Efficacy and safety of brigimadlin (BI 907828), an MDM2– ... Brigimadlin showed a manageable safety profile and encouraging preliminary efficacy in pts with BTC, with 7 PRs and 7 SDs in 16 pts.

7. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT288/742536/Abstract-CT288-Brightline-4-A-phase-3-open-label

Abstract CT288: Brightline-4: A phase 3 open-label, single ... Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in ...