Breakthrough Clinical Results
Boehringer Ingelheim will present data from two early-stage clinical trials investigating their SIRPα inhibitors, BI 765063 and BI 770371, at the 2025 ASCO Annual Meeting. BI 765063, in combination with ezabenlimab and cetuximab, showed a manageable safety profile and potential efficacy in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). BI 770371 demonstrated good tolerability alone and in combination with ezabenlimab in patients with advanced solid tumors. Both drugs aim to block the 'don't eat me' signal used by cancer cells to evade the immune system. Boehringer Ingelheim is developing these antibodies in partnership with OSE Immunotherapeutics.
Key Highlights
- Early clinical data on two SIRPα inhibitors (BI 765063 and BI 770371) will be presented at ASCO 2025.
- BI 765063 showed a manageable safety profile and potential efficacy in combination therapy for HNSCC.
- BI 770371 demonstrated good tolerability alone and in combination with a PD-1 inhibitor in patients with advanced solid tumors.
- Both drugs aim to enhance the immune system's ability to recognize and destroy cancer cells.
Incidence and Prevalence
Latest Estimates of Incidence and Prevalence of Head and Neck Squamous Cell Carcinoma Globally
Head and neck squamous cell carcinoma (HNSCC) represents a significant global health burden, ranking as the sixth most common cancer worldwide. Approximately 90-90% of all head and neck cancers are classified as squamous cell carcinoma.
Global Impact
HNSCC accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually on a global scale. According to the GLOBOCAN 2020 database, the incidence rates of multiple types of head and neck cancer were positively associated with Human Development Index (HDI) tiers.
Regional Variations
The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. Oral squamous cell carcinoma (OSCC) is associated with a high death rate of around 50% in some regions of the world.
United States Statistics
In the United States, HNSCC accounts for approximately 2% of all cancers and 2% of cancer deaths. In 2001, a total of 75,000 cases of head and neck cancer were diagnosed in the United States, with 30,000 deaths from head and neck cancer that same year.
Changing Trends
Despite falls in alcohol consumption and reduction in smoking, the incidence rate of new disease continues to rise. Specifically, incidence is rising in: - Thyroid (up 52%) - Bone (43%) - Soft tissues (20%) - Salivary (20%) - Tongue (16%) - Tonsil (12%) - Nose (12%)
Conversely, incidence is falling in: - Lip (down 58%) - Hypopharynx (35%) - Cervical esophagus (32%) - Oropharyngeal mucosa (26%) - Larynx (26%)
HPV-Related Cases
The incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. While traditional treatments include surgery, radiotherapy, and immunotherapy, several key mechanisms of action (MoA) have emerged in recent years based on research publications.
Immune Checkpoint Inhibitors
One of the most significant advances in HNSCC treatment involves immune checkpoint inhibitors targeting PD-1/PD-L1 pathways, which have become the standard of care in HNSCC. Research findings indicate that in tongue SCCs, PD-L1 upregulation correlates with more advanced disease stage and shorter disease-free survival. This suggests that PD-1/PD-L1 inhibitors could serve as potential adjuvant therapy specifically for tongue SCCs that show PD-L1 upregulation.
T-Cell Activation Markers
The presence and activity of T-cells within the tumor microenvironment significantly impact treatment outcomes. Studies show that T-cell activation (characterized by high expression of CD4, CD8, and FoxP3) is associated with: - Better response to radiation therapy - Favorable survival in advanced head and neck cancer
Specifically: - High CD4 expression correlates with complete response after radiation - High CD8 tumor-infiltrating lymphocyte counts are linked to absence of tumor relapse and improved disease-free survival - Tumors with high FoxP3 T regulatory infiltration demonstrate better disease-free survival
Novel Targeted Approaches
Several innovative targeted approaches are showing promise:
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Gold nanoparticles (AuNPs) combined with cetuximab (an IgG1 monoclonal antibody targeting EGFR) and radiotherapy demonstrate enhanced antitumor effects
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Endoplasmic reticulum stress (ERS)-related signature comprising six genes (ASNS, EXOSC6, BAK1, TPP1, EXOSC8, and TATDN2) serves as a predictor for prognosis and immunotherapy response
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Tumor-associated macrophages (TAMs) represent a promising therapeutic target with two main approaches:
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CSF-1/CSF-1R inhibitors to block TAMs
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Strategies to reprogram TAMs from M2 protumoral phenotype toward M1 antitumoral phenotype
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Tyrosine kinase inhibitors (TKIs) and mTOR inhibitors affecting apoptosis-related proteins in both HPV-dependent and HPV-negative squamous cancer
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Certain neuropeptides with antitumor properties acting as tumor suppressors and immunomodulators
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Long non-coding RNAs (lncRNAs) such as AL365361.1 and PCED1B-AS1 involved in tumor immune microenvironment modification
These emerging mechanisms of action represent significant advancements in understanding HNSCC biology and developing more effective, targeted treatment approaches.
Drug used in other indications
BI 765063, Ezabenlimab, and Cetuximab Trials
Cetuximab Indications Beyond Head and Neck Squamous Cell Carcinoma
Cetuximab is being trialed or used in several indications beyond Head and neck squamous cell carcinoma (HNSCC), including:
- Recurrent/metastatic squamous cell carcinoma (SCC), including soft-tissue sarcoma where it was studied in combination with avelumab
- Used in combination with platinum-based chemotherapy for recurrent or metastatic disease
- Being evaluated in combination with immune checkpoint inhibitors in both locally advanced and recurrent/metastatic settings due to cetuximab-mediated immunogenicity through antibody dependent cell cytotoxicity (ADCC)
- Studied in combination with docetaxel/cisplatin/5-fluorouracil regimen as second-line therapy
- Being investigated in conjunction with radiation therapy for patients unsuitable for standard chemoradiotherapy
- Used in clinical trials exploring its efficacy when combined with tyrosine kinase inhibitors
Regarding BI 765063 and Ezabenlimab
The provided context does not contain any information about: - BI 765063 indications - Ezabenlimab indications - BI 765063 trial intervention models - Ezabenlimab trial intervention models - Cetuximab trial intervention models