FDA Approval of Keytruda for Head and Neck Cancer Highlights Potential for CEL-SCI's Multikine in PD-L1 Negative Patients

Global Incidence and Mortality Trends (2022):

• GLOBOCAN 2022 Estimates:

• Males: Lung cancer (1.57 million new cases), followed by prostate cancer (1.47 million).

• Females: Breast cancer (2.30 million new cases), followed by lung cancer (0.91 million) and cervical cancer (0.66 million).

• Leading cause of cancer death: Lung cancer in both males (1.23 million deaths) and females (0.67 million deaths).

Incidence Trends by Subsite and Region:

• Overall HNSCC Incidence: Declining overall, especially for non-oropharyngeal HNSCC (larynx, oral cavity, hypopharynx, nasopharynx, nasal cavity). Significant declines observed in both men and women.
• Oropharyngeal Squamous Cell Carcinoma (OPSCC): Increasing incidence, particularly between 2000 and 2014. More pronounced increase in men from 2001 to 2014 (APC 2.7) compared to a stable/slightly decreasing trend in women.
• Non-Oropharyngeal HNSCC: Significant declines in incidence across all sites for both men and women.
• Racial Disparities: Decreases in non-oropharyngeal HNSCC risk were particularly large for Black men and women. While HNSCC incidence was historically highest among Black individuals, it has been higher among White individuals since 2009.

• Global Trends (1990-2017):

• Larynx and nasopharyngeal cancer incidence decreased.

• Oropharyngeal and lip/oral cavity cancer incidence increased.

• Incidence remains markedly higher in men than women.

• Highest incidence rates in South Asia, followed by Europe, North America, and Australasia.

• Tongue SCC: General increase in incidence worldwide, with some regions showing a shift toward younger patients and women.
• Small Cell Carcinoma of the Head and Neck (SmCCHN): Rare and aggressive, with worse survival and more advanced stage at presentation compared to squamous cell carcinoma of the head and neck (SCCHN).

• Cutaneous Squamous Cell Carcinoma (cSCC):

• Increasing incidence, with a disproportionate increase relative to basal cell carcinoma (BCC) and a larger increase in women.

• Anatomical distribution shifting from head and neck to extremities.

• Global increase in incidence (345%) since 1990, with the highest age-standardized prevalence rate in high Sociodemographic Index (SDI) regions and the highest age-standardized mortality and disability-adjusted life years in middle SDI regions.

Prevalence Data:

• Limited global prevalence data for HNSCC specifically. Most studies focus on incidence and mortality.
• cSCC: Global prevalence of 2,275,834 cases in 2021.
• Neck Pain: Global age-standardized point prevalence rate of 3551.1 per 100,000 in 2017, with no significant change between 1990 and 2017.

Note: These estimates represent the latest available data from various sources, including GLOBOCAN 2022 and the Global Burden of Disease Study. It's important to note that data availability and quality can vary across regions and subsites, which can affect the accuracy of estimates.

Unmet Needs in Head and Neck Squamous Cell Carcinoma (HNSCC)

Several key unmet needs and target populations have been identified in recent research on Head and Neck Squamous Cell Carcinoma (HNSCC):

• HPV-negative R/M HNSCC: Patients with recurrent and/or metastatic (R/M) HPV-negative HNSCC face poor survival rates. Unmet needs include effective therapies to address treatment resistance and disease progression, particularly targeting mechanisms like crosstalk between EGFR and c-MET pathways.

• HNSCC Survivorship: A growing number of HNC patients are surviving, leading to increased focus on survivorship care. Unmet needs include addressing fear of recurrence (for both patients and partners), coordinating care among physicians, meeting diverse patient needs within multidisciplinary teams, ensuring access to high-quality patient-centered care, and improving communication and care transitions with primary care physicians.

• Targeted Therapies: There's a need for more effective, less toxic, and highly specific targeted therapies for HNSCC. Research focuses on understanding HNSCC biology and immunobiology to identify predictive/prognostic biomarkers that can guide development of such therapies.

• Clinical Trial Design for HER2+ Breast Cancer with Brain Metastases (BM): While not strictly HNSCC, this relates to the broader challenge of managing head and neck malignancies. There's a need for standardized clinical trial designs for HER2+ metastatic breast cancer patients with BM, including consistent eligibility criteria, CNS-focused endpoints, and robust statistical analysis. This is crucial for interpreting treatment landscape and ensuring access to effective therapies for all BM types.

Specific Patient Populations:

• Rural HNSCC Patients: Studies show unique unmet psychosocial needs in rural HNSCC patients related to finances, travel, and accessing care. More research is needed to determine if these needs are greater than those of urban patients and whether they stem from general rural challenges or are cancer-specific.

Quantifiable Gaps:

• Up to 60-65% of HNC survivors report at least one unmet need in survivorship care.
• 90% of head and neck cancers are squamous cell carcinomas (HNSCC), highlighting the significance of addressing unmet needs within this specific subtype.
• Only two trials (HER2CLIMB and DEBBRAH) included patients with both active and stable brain metastases in the context of HER2+ metastatic breast cancer, demonstrating a gap in clinical trial design for this population.