Bringing focus to unmet needs in biliary tract and pancreatic cancers with the Brightline-2 clinical trial

Biliary tract cancers (BTCs) and pancreatic cancer are rare and aggressive cancers historically associated with poor prognoses. People living with BTCs face long odds with an estimated five-year overall survival rate of less than 20%. Similarly, patients with pancreatic cancer face a five-year relative survival rate of just 11%¹.

The outlook for these devastating cancers is dire. We are still in the early stages of understanding genomic mutations that may drive them, and the situation is compounded by delays in testing and diagnosis. This can result in patients typically presenting with more advanced stages of disease. There is also limited availability of treatment options, particularly after the failure of first-line therapy or disease progression.

Boehringer Ingelheim has made a generational commitment to driving scientific innovation, which is reflected by our robust pipeline of cancer cell-directed and immuno-oncology investigational therapies. We are therefore pleased to have started enrolling patients in the Brightline-2 clinical trial (Clinicaltrials.gov identifier: NCT05512377) studying brigimadlin (BI 907828, an investigational MDM2-p53 antagonist) for people with advanced cancer in the biliary tract or pancreas, featuring MDM2 amplification and tumor protein 53 (TP53) wild-type status, confirmed through molecular profiling. 

“For people living with biliary tract and pancreatic cancers who have such limited treatment options, it's essential to recognize any and all progress toward advancements in treatment and diagnostics. Clinical trials are vital for bringing new solutions to patients. The Cholangiocarcinoma Foundation is encouraged to hear of Boehringer Ingelheim's phase II clinical trial for biliary tract and pancreatic cancers. We hope to see progress in treatment and diagnostic measures to improve patients' outcomes from these devastating diseases”, said Melinda Bachini, Director of Patient Services, Cholangiocarcinoma Foundation. 

Brightline-2 is a Phase IIa/IIb trial investigating BI 907828 as monotherapy for the treatment of locally advanced or metastatic MDM2-amplified TP53 wild-type biliary tract adenocarcinoma, pancreatic ductal adenocarcinoma, or other selected solid tumors that are not suitable for targeted treatment and/or standard of care therapy. In this investigation of BI 907828, an oral, small molecule MDM2-p53 antagonist, around 100 patients in total are expected to be enrolled across Phases lla and IIb of the trial in North America, Asia Pacific, and Europe. 

In Q2 2023, the U.S. Food and Drug Administration granted brigimadlin (BI 907828) Orphan Drug Designation for the potential treatment of biliary tract cancer. This achievement marks a positive step towards delivering meaningful advances for the treatment of this rare cancer.

This compound is an investigational agent and has not been approved for use by any regulatory authority including the U.S. Food and Drug Administration (FDA). The efficacy and safety of this investigational compound have not been established.

Progressing Research Through Strategic Partnerships 

We are taking a collaborative approach with Brightline-2 and are partnering with Foundation Medicine, a leader in molecular profiling, for companion diagnostic development. This collaboration was established because high quality, well-validated genomic testing is critical to identify patients with MDM2 amplified biliary tract adenocarcinoma, who may be appropriate for this future treatment option. The partnership aims to develop Foundation Medicine’s tissue-based comprehensive genomic profiling test, FoundationOne®CDx, as a companion diagnostic for brigimadlin (BI 907828) in the United States, European Union, and Japan.

Sanket Agrawal, Head of Biopharma at Foundation Medicine said, “Foundation Medicine is proud to partner with Boehringer Ingelheim to help gain a deeper understanding of the complex genomics, such as MDM2 amplifications and TP53 status, that drive BTCs and pancreatic cancer. Our hope is that this global partnership leads to promising advancements in care for people living with these cancers who currently continue to face limited treatment options.”

In the United States, the Brightline-2 trial is also being managed in partnership with Tempus and other next-generation sequencing companies that analyze clinical and molecular data to identify actionable clinical trial options for people living with cancer. Ultimately, the goal of these partnerships is to help bring this trial to rural and underserved communities. 

Gaining a Greater Understanding of the MDM2-p53 Pathway 

Through this trial, we are aiming to expand our knowledge, and that of the oncology community, about the role of the MDM2-p53 pathway in cancer development. Evasion of cell-cycle arrest and cell death by inactivation of p53 is a key mechanism by which tumors promote survival and tumor growth. The MDM2 oncoprotein is a critical negative regulator of p53; MDM2 amplification and/or overexpression of MDM2 drives tumor proliferation. BI 907828 blocks the interaction between the tumor suppressor p53 and MDM2, leading to stabilization of p53, TP53 target gene induction, causing cell-cycle arrest and apoptosis in tumor cells with wild-type TP53 status. Prevalence of MDM2 amplification varies depending on tumor types, and it is considered to be approximately 5-7% in BTCs. 

At Boehringer Ingelheim, we take a diligent and broad approach in some of the most difficult, but potentially most impactful, areas of cancer. Our hope is that through these collaborations, we will be able to address the treatment challenges these patients continue to face. 

For information on BI 907828 in dedifferentiated liposarcoma: 

Brightline-1

• Learn about our MDM2-p53 antagonist and Brightline-1 clinical trial 

• Visit the HCP Trial Site 

Boehringer Ingelheim 

Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. More than 52,000 employees serve over 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com   

Boehringer Ingelheim in Oncology

We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Our generational commitment to driving scientific innovation is reflected by our robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. We are taking a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research.  

Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Read more here. 

Date published: 19th January 2023, updated July 2023

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