Brigimadlin for Liposarcoma

Recruiting at 76 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

138 Participants Needed

Trial Summary

What is the purpose of this trial?

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 MDM2. The purpose of this study is to find out whether a medicine called brigimadlin (BI 907828) is tolerated by and helps people with DDLPS. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Participants take brigimadlin as a tablet once every 3 weeks. Participants may continue to take brigimadlin as long as they benefit from treatment and can tolerate it. They visit the study site regularly. At the study site, doctors regularly check participants' health and take note of any unwanted effects. The doctors also regularly check tumour size.

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.

What data supports the effectiveness of the drug Brigimadlin for treating liposarcoma?

The drug BI 907828, which is similar to Brigimadlin, has shown promising results in early studies for treating dedifferentiated liposarcoma (DDLPS) by targeting the MDM2-p53 interaction, which is often amplified in these tumors. This suggests that Brigimadlin, if it works similarly, might also be effective for this condition. ^{1 2 3 4 5}

What safety data exists for Brigimadlin (BI 907828) in humans?

Brigimadlin, also known as BI 907828, has been studied in early-phase trials for patients with solid tumors, including liposarcoma. These studies are ongoing, and while they show promising activity, detailed safety data specific to humans is still being gathered. ^{1 5 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England 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. [2022]

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

The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Adipogenesis induces growth inhibition of dedifferentiated liposarcoma. [2021]

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

An experimental model for the study of well-differentiated and dedifferentiated liposarcoma; deregulation of targetable tyrosine kinase receptors. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Brightline-1: phase II/III trial of the MDM2-p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS. [2023]

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

FDA Approval Summary: Eribulin for Patients with Unresectable or Metastatic Liposarcoma Who Have Received a Prior Anthracycline-Containing Regimen. [2023]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Overview of systemic therapy options in liposarcoma, with a focus on the activity of selinexor, a selective inhibitor of nuclear export in dedifferentiated liposarcoma. [2022]