Breakthrough Clinical Results
Bicara Therapeutics announced updated interim data from a Phase 1/1b clinical trial of ficerafusp alfa in combination with pembrolizumab for first-line recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). The data, presented at the 2025 ASCO Annual Meeting, showed an encouraging objective response rate of 64% in HPV-negative patients, with a median progression-free survival of 9.8 months and a 12-month overall survival rate of 61%. The median overall survival and duration of response had not yet been reached, with median overall survival exceeding 20 months. Ficerafusp alfa is a first-in-class bifunctional antibody designed to enhance tumor penetration. A company conference call is scheduled to discuss the full dataset.
Key Highlights
- 64% objective response rate in HPV-negative patients with 1L R/M HNSCC
- Median progression-free survival of 9.8 months in HPV-negative patients
- 12-month overall survival rate of 61% in HPV-negative patients
- Median overall survival exceeding 20 months in HPV-negative patients
Incidence and Prevalence
Global Incidence and Prevalence of Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. More than 90-95% of head and neck cancers are squamous cell carcinomas.
Global Statistics
- HNSCC accounts for 2.5% of all new cancer cases globally
- It represents 1.9% of all cancer deaths annually worldwide
- The mortality rate is approximately 50% in some regions of the world
- The incidence rate of new HNSCC continues to rise, despite falls in alcohol consumption and reduction in smoking
Regional Variations
- The incidence rate of oral cancer varies widely throughout the world
- There is an evident prevalence in South Asian countries
- In the United States specifically, HNSCC accounts for approximately 2% of all cancers and 2% of cancer deaths
Trends in HNSCC
- The incidence of HPV-related oral squamous cell carcinoma (OSCC) appears to be on the rise
- HPV-unrelated OSCC tends to have stabilized in the past decades
Despite changes in risk factor exposure such as smoking and alcohol consumption, HNSCC remains a significant global health concern with high mortality rates and increasing incidence in certain populations.
Key Unmet Needs and Targeted Populations for Head and Neck Squamous Cell Carcinoma
Disease Characteristics and Burden
- HNSCC is the sixth most common cause of cancer death in the United States
- HNSCC has a significant global burden with poor survival rates
- 5-year survival rate remains low at only 60%
- HNSCC has high rates of invasion and metastasis
- Treatment failure is potentially lethal due to local recurrence, regional lymph node metastasis, and distant metastasis
Treatment Challenges
- Current treatments have remained unsatisfactory with high death rates
- Treatment of locally advanced disease is associated with significant acute side effects and can lead to chronic disabilities
- Prognosis of recurrent or metastatic disease is very poor
- Drug-resistance is a significant challenge requiring novel and effective chemotherapeutic approaches
- Treatment-resistant cancer cells represent one of the most significant obstacles to developing effective cancer treatment options
Specific Populations with Unmet Needs
- Patients with recurrent and/or metastatic HNSCC
- Patients with rare histologic types of head and neck cancer such as adenocarcinoma and adenoid cystic carcinoma
- Adenoid cystic carcinoma patients who have traditionally been considered chemotherapy resistant
- HIV-positive head and neck cancer patients
- Patients requiring lipotransfer as part of secondary surgical procedures
- Patients eligible for Serious Illness Conversations (SIC)
Molecular Targets and Biomarkers
- EGFR (Epidermal Growth Factor Receptor) is overexpressed in 90% of HNSCC patients and is an attractive therapeutic target
- p38 MAPK isoforms have potential as diagnostic and prognostic markers for HNSCC
- lncRNAs and miRNAs could be used as diagnostic biomarkers, but require further investigation
- The tumor microenvironment and its cellular components (including mesenchymal stromal cells) require further study
- Circulating tumor cells (CTCs) could serve as surrogate biomarkers for metastasis
Therapeutic Approaches Requiring Further Development
- Targeted therapies including EGFR inhibitors, multi-tyrosine kinase inhibitors, and p38δ inhibitors
- Better understanding of autophagy's role in EGFR inhibitor-induced cancer suppression
- Investigation of novel compounds like Cyclosporine A (CsA) to overcome drug resistance
- Further validation of molecular pathway targets including PI3K-Akt, MAPK, and Wnt signaling pathways
- Need for validated biomarkers to predict clinical benefit and resistance to anti-EGFR therapy
- Need for new agents and treatment strategies beyond cetuximab
- Need for improved understanding of therapy resistance mechanisms
Population-Specific Research
- Patients with different molecular subtypes identified through cell-cell communication gene signatures
- Research involving peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators
- Studies focusing on patients eligible for detailed biopsies to identify markers for selecting specific patient populations
Recent Studies
Recent Studies for Head and Neck Squamous Cell Carcinoma
MUC1 CAR-T Therapy Study
This study examined MUC1 as a target for CAR-T therapy in head and neck squamous cell carcinoma (HNSCC). Researchers constructed a second-generation CAR and validated cytotoxic function in vitro. They discovered that exogenous addition of human IL22 recombinant protein could increase MUC1 expression and enhance T cell function. Additionally, they developed a fourth-generation CAR that secretes IL22. The CAR-MUC1-IL22 T cells demonstrated stronger and more effective cytotoxic function against MUC1+ HNSCC cells. This research demonstrates the potential effectiveness of CAR-T therapy for HNSCC patients.
Reirradiation Study
A study analyzed records of 75 consecutive patients with recurrent or second primary head and neck cancer treated between August 2005-December 2013. Key outcomes included: - Median overall survival: 29.5 months - Cancer-specific survival: 33.6 months - Median local control: 21.7 months - Progression-free survival: 16.2 months
Positive prognostic factors included: - Age <70 years - Karnofsky Performance Status >90 - ≤2 comorbidities - Biological equivalent dose >72 Gy
Safety concerns included a 6.7% rate of fatal treatment-related adverse events (3 carotid blowout, 1 soft tissue necrosis, 1 thromboembolic event). Planning target volume >221 mL was associated with worse local control and progression-free survival. The study confirmed the role and outcomes of reirradiation in HNSCC.
Cetuximab (Erbitux) Study
Cetuximab use in HNSCC is associated with clinical benefit and in some cases survival. Combination therapy of molecular targeted agents with chemoradiation shows early promising results but with increased toxicity.
Guggulsterone Systematic Review and Meta-analysis
This systematic review included 40 articles, with 23 included in the meta-analysis. The search across 7 databases yielded 55,280 studies. Guggulsterone significantly affected HNSCC (cell lines SCC4, UM-22b, 1483) by inducing apoptotic pathways, inhibiting cell proliferation, and regulating expression of genes involved in apoptosis. Studies reported: - 11 studies showed apoptotic effect at t = 24 hours with pooled odds ratio of 3.984 - 12 studies used Guggulsterone for t > 24 hours with odds ratio of 11.171
Psychological Interventions for HNC
Various psychological interventions have been studied for HNC patients: - Psycho-education (7 studies) - Cognitive-behavioural therapy (7 studies) - Communication skills training (1 study) - Support group (1 study)
The review found most support for psycho-education, with 3 out of 5 studies finding at least some effect. Research showed it is feasible to recruit HNC patients to psychological interventions and evaluate their progress.
Drug used in other indications
Based on the provided context, there is no information about Ficerafusp alfa and pembrolizumab being trialed for indications other than Head and neck squamous cell carcinoma (HNSCC). The context does not mention Ficerafusp alfa at all in any of the reference materials. While pembrolizumab is mentioned as having a good safety profile in gastro-oesophageal cancer and urothelial cancer compared to non-ICI groups, the context does not specifically discuss ongoing trials for these indications.
Additionally, there is no information provided about intervention models for any trials involving either Ficerafusp alfa or pembrolizumab in the context.