Why cancer care is personal for us

Oncology has one of the highest unmet needs in the entire healthcare industry.^{1, 2} Despite major treatment advances in recent years, people are still dying from cancer earlier than they should.^3,4 Our communities are relying on us as researchers, academics and clinicians to continue delivering meaningful advances in cancer research and care.  

Our approach

At Boehringer Ingelheim, we have made a generational commitment to transforming cancer care, with the ultimate goal of curing a range of cancers.  
 
Meeting this goal requires a diversity of minds. Together with our collaborative network of research partners, we are constantly working on a robust pipeline of pre-clinical and clinical stage investigational therapies, with diverse modes of action. We are taking a diligent and broad approach in some of the most challenging, but potentially most impactful, areas of cancer research. We have defined a handful of investigational therapies that follow an accelerated development path, with the goal of bringing them to market, and thus to people living with cancer, as fast as we can. 

Our pipeline

We are developing platforms, such as T cell engagers (TcEs), oncolytic viruses, and cancer vaccines, which have the potential to turn cold tumors hot, extending the benefits of immunotherapy to more people. In parallel, within the area of cancer cell-directed treatments, we are investigating the key drivers of cancer, such as p53 and KRAS. We believe that it is the smart combination of these approaches that could offer the greatest benefit for people living with cancer.

MDM2

An example of our cancer-cell directed pipeline research is our investigational MDM2-p53 antagonist, brigimadlin (also known as BI 907828). p53 acts as a tumor suppressor, driving tumor cell death. MDM2 is the primary negative regulator inhibiting its tumor suppressor activity. Brigimadlin is a highly potent, oral, small molecule compound that inhibits the interaction between MDM2 and p53, restoring p53 wild type function. 

This antagonist is showing promising preliminary signals from a phase I study in people with an ultra-rare form of soft tissue sarcoma, called dedifferentiated liposarcoma (DDLPS). It is currently being investigated in our clinical trial called Brightline-1 (clinicaltrials.gov identifier: NCT05218499). The U.S. Food and Drug Administration (FDA) provided Fast Track Designation for the investigation of brigimadlin in DDLPS. People affected by this devastating cancer have had no new first-line treatment options in 45 years, and now, we are working hard to provide more therapeutic options to potentially improve their lives.  

In addition to the trial in people with DDLPS, our Brightline-2 trial (Clinicaltrials.gov identifier: NCT05512377) is recruiting in other cancers such as biliary tract, pancreatic and selected solid tumor cancers.

HER2

Another example is zongertinib (also known as BI 1810631), an irreversible HER2-selective tyrosine kinase inhibitor (TKI). HER2 is a member of the ErbB family of receptor tyrosine kinases. Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death, and promotion of tumor growth and spread. HER2 gene alterations are seen across a number of different cancer types. Prevalence of HER2 mutations in non-small cell lung cancer (NSCLC) is estimated to be between 2-6% - approximately 40.000 new cases with HER2-mutated NSCLC per year. 

Zongertinib is currently being investigated in a phase I clinical trial (clinicaltrials.gov identifier: NCT04886804). In line with our pipeline approach, once we saw a first positive signal, we quickly increased our efforts to accelerate this compound development so that we can enroll patients into this clinical trial sooner. 

In 2023, Zongertinib was granted Fast Track Designation by the U.S. FDA as an investigational oral treatment for people with NSCLC whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

DLL3

An example of our immunotherapy research is BI 764532, an investigational T-cell engager. The DLL3 protein as a new potential target was identified through the Oxford BioTherapeutics’ OGAP^® platform. BI 764532 is being investigated in a phase II trial (clinicaltrials.gov identifier: NCT05882058) for the treatment of people living with extensive stage small cell lung cancer (ES-SCLC), extrapulmonary neuroendocrine carcinomas (epNEC), and large-cell neuroendocrine carcinoma of the lung (LCNEC-Lung).^6,7 BI 764532 is an investigational T-cell engager that might selectively redirect T cells towards cancer cells expressing the DLL3 protein, potentially resulting in the destruction of SCLC or other neuroendocrine carcinomas (NEC) tumors by the body's own immune system.

As of November 2023, the U.S. FDA granted BI 764532 with:

• Fast Track designations in advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC-Lung) expressing DLL3 whose disease has progressed following at least one prior line of treatment including platinum-based chemotherapy.
• Orphan Drug designation for SCLC.
• Fast Track designation in ES-SCLC with disease progression following at least two prior lines of treatment including platinum-based chemotherapy, and for epNEC with advanced or metastatic disease following at least one prior line of treatment including platinum-based chemotherapy.

Delta-like ligand 3 (DLL3) is a protein that is expressed specifically on the surface of up to 85% of SCLC tumor cells and around 77% of NECs.^8,9 In normal tissue, DLL3 is minimally expressed, which makes it an ideal therapeutic target.

These compounds are investigational agents and they have not been approved for use by any regulatory authority including the U.S. Food and Drug Administration (FDA). The efficacy and safety of these investigational compounds have not been established. 

Cancer is the pandemic of the century, with the most potential in terms of innovation.^8,9 By being innovative in our research and constantly pushing forward, we can make a difference – with a goal of delivering life-changing treatments that seek to keep families together.  

References

1. Albrecht, B. et al. (2020) Delivering innovation: 2020 oncology market outlook. McKinsey & Company. Available at: https://www.mckinsey.com/industries/life-sciences/our-insights/delivering-innovation-2020-oncology-market-outlook (Accessed: December 13, 2022).  
2. Unmet needs in 2020: Exploring What Innovation Means Today. In Vivo. Available at: https://invivo.pharmaintelligence.informa.com/-/media/supporting-documents/in-vivo-issue-pdfs/iv2003_lrs.pdf (Accessed: December 13, 2022).  
3. Roberts LR et al. The Oncologist 2022; 27(9): 760-767. 
4. Sapio L et al. Int. J. Mol. Sci. 2022; 23(10): 5296. 
5. Xin Yu et al. Front Oncol. 2022; 12: 860313.
6. Wermke: BI 764532 ph 1 trial in progress (ASCO 2020 poster) – data on file.
7. Hazini A., J Immunotherapy Cancer 2021.
8. Kaidar-Person O et al. Obes Surg. 2011; 21(11): 1792–1797.
9. Sharma P et al. Medical Oncology 2022; 39(76). 

Date published: 2nd February 2023, updated November 2023