Breakthrough Clinical Results

Boehringer Ingelheim announced that it will present new clinical data from two early-stage trials investigating SIRPα inhibitors at the 2025 ASCO Annual Meeting. The Phase 1b trial of BI 765063, a SIRPα monoclonal antibody, in combination with ezabenlimab and cetuximab showed a manageable safety profile and preliminary signs of immune activation and antitumor activity in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). A separate Phase 1 trial of BI 770371, a next-generation SIRPα monoclonal antibody, alone and in combination with ezabenlimab, demonstrated good tolerability in patients with advanced solid tumors. Both BI 765063 and BI 770371 aim to block the 'don't eat me' signal used by cancer cells to evade the immune system, thereby enhancing immune cell recognition and destruction of tumor cells. BI 770371 will proceed to a Phase 1b study in first-line R/M HNSCC patients.

Incidence and Prevalence

Global Incidence and Prevalence of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) represents 90-95% of all head and neck cancers, which are among the most common cancers worldwide.

According to the GLOBOCAN 2020 database, head and neck cancers affect 650,000 people and cause 350,000 deaths per year globally. This makes head and neck cancer the sixth most common cancer by incidence and eighth by cancer-related death worldwide.

In the United States, head and neck cancer accounts for approximately 2% of all cancers and 2% of cancer deaths.

Oral cancer is the most common type of head and neck cancer, with more than 90% of oral cancers being oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is attributed to the low response rate to current therapeutic drugs. In some regions of the world, OSCC is associated with a high death rate of around 50%.

The incidence rates of multiple types of head and neck cancer are positively associated with Human Development Index (HDI) tiers.

Notably, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC has stabilized in the past decades.

Emerging Mechanism of Action

Study Design Parameters

Study Design Parameters and Endpoints in Key Trials for Head and Neck Squamous Cell Carcinoma

Study Design Parameters

Several pivotal clinical trials have been conducted to evaluate treatments for Head and Neck Squamous Cell Carcinoma (HNSCC), each with distinct design parameters:

PET-Neck Trial

• Randomized trial design

• Faced recruitment challenges including:

• Patient consent refusal due to treatment preference

• Aversion to randomization

• Excess complexity/amount of information provided

• Lack of clinic time

Biomarker Predictive Study

• Included 28 patients with non-operable tumors of the oral cavity or oropharynx
• Conducted short-term culture of tumor fragments irradiated ex vivo
• Investigated biomarkers including CD44, pATM, and γ-H2AX

Bevacizumab Study

• Evaluated anti-tumor effects of bevacizumab on HNSCC
• Used both in vitro testing against HNSCC cell lines and in vivo testing with HNSCC xenografts in mice
• Assessed combination therapy of bevacizumab-paclitaxel

VE-822 (p-ATR inhibitor) Study

• Evaluated combination with cisplatin in cisplatin-resistant and sensitive HNSCC cell lines
• Methods included comet assay, western blot, CCK-8 test
• Validated in subcutaneous xenograft models of nude mice

RADPLAT Trial

• Studied 250 patients with advanced head and neck cancer
• Treatment with intra-arterial cisplatin and radiotherapy
• Excluded patients who didn't complete protocol or were unavailable for follow-up

Recurrent-Metastatic HNSCC Trial

• Included 40 patients divided into two groups:

• 14 long-progression-free survival (PFS) patients

• 26 short-PFS patients

• Examined gene expression of pretreatment samples

Gefitinib with Cisplatin/Radiotherapy Study

• Recruited 31 patients with locally advanced and easily accessible primary tumor sites
• Gefitinib was started 3 weeks before cisplatin/concurrent radiotherapy
• Continued during CTRT and for 4 months as consolidation

Trial Endpoints

Primary Endpoints

• Overall survival (in De-ESCALaTE and RTOG 1016 studies)
• Progression-free survival (in De-ESCALaTE and RTOG 1016 studies)

Secondary and Exploratory Endpoints

• Biomarker analysis:

• CD44 (stemness status)

• pATM and γ-H2AX (DNA damage response)

• EGFR protein expression, FISH and mutational status

• MMP11 protein expression

• Response rates:

• Complete response (CR)

• Partial response (PR)

• Stable disease (SD)

• Progressive disease (PD)

• Biological effects:

• Blood vessel density

• Apoptotic index

• Cell proliferation

• Migration

• Colony formation

• Drug resistance mechanisms:

• Protein levels of HER family receptors (EGFR, HER2, HER3)

• Downstream activation of AKT and MAPK

• Safety and toxicity evaluation

In immunotherapy trials, nivolumab and pembrolizumab were approved as second-line treatments for platinum-refractory recurrent/metastatic HNSCC, while atezolizumab and durvalumab showed similar benefits in phase Ia and II studies.

Drug used in other indications

Based on the provided context, there is no information available about:

• BI 765063 being trialled for Head and neck squamous cell carcinoma or any other indications
• Ezabenlimab being trialled for Head and neck squamous cell carcinoma or any other indications
• Cetuximab being trialled for indications other than Head and neck squamous cell carcinoma

Additionally, the context does not provide any information about the intervention models for clinical trials involving these medications.

The context only mentions cetuximab in relation to Head and neck squamous cell carcinoma (HNSCC), non-melanoma skin cancer, and as a general EGFR inhibitor, but does not specifically discuss clinical trials for indications beyond HNSCC.