For those with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), the first patients have been enrolled in the FORTIFI-HN01 study, which is a phase 2/3 trial of ficerafusp alfa (BCA101) in combination with Keytruda (pembrolizumab) in first-line treatment, according to a news release from the drug’s manufacturer, Bicara Therapeutics.
“Incidence is rising, yet survival rates remain low, particularly for patients with human papillomavirus [HPV]-negative disease, underscoring the urgent need for innovative treatment options,” Dr. John Kaczmar of Medical University of South Carolina Hollings Cancer Center, said in the news release. “I’m encouraged by the early signs of clinical activity in these patients we have seen treated with ficerafusp alfa and hopeful it will help address this area of significant unmet need.”
According to the release, ficerafusp alfa is a first-in-class bifunctional antibody that targets epidermal growth factor receptor (EGFR) and binds to human transforming growth factor beta (TGF-β), offering potential anti-tumor activity by blocking EGFR survival and proliferation and TGF-β signaling in the tumor microenvironment.
Glossary:
Mucosal epithelium: layer of epithelial cells lining mucous membranes.
Metastatic: cancer spreading to other parts of the body.
Cachexia: muscle wasting and weight loss in chronic disease.
Bifunctional antibody: antibody that binds two targets.
Tumor microenvironment: surrounding cells and molecules influencing tumor growth.
PD-L1 CPS of 1 or higher: score indicating PD-L1 expression, predicting immune therapy response.
Overall response rate: percentage of patients showing tumor shrinkage.
Overall survival: time from treatment start to death from any cause.
Progression-free survival: time without cancer progression.
Duration of response: time cancer remains controlled after treatment.
Pharmacokinetic data: drug absorption, distribution, metabolism and excretion data.
Pharmacodynamic data: drug effects and therapeutic mechanisms.
FORTIFI-HN01 is a phase 2/3 global trial evaluating a treatment in about 650 patients with recurrent or metastatic HNSCC, excluding those with HPV-positive oropharyngeal squamous cell carcinoma. Participants must have a PD-L1 combined positive score (CPS) of 1 or higher and no prior systemic therapy in the recurrent or metastatic setting. The study’s primary end goals are overall response rate and overall survival, with potential for accelerated and full approval filings. Secondary end goals include progression-free survival and duration of response.
According to clinicaltrials.gov, phase 2 of the study will identify an optimal biologic dose (OBD) of ficerafusp alfa, supported by safety, tolerability, pharmacokinetic, pharmacodynamic and efficacy data. Eligible subjects will be randomized to one of three treatment groups. The primary goal of the phase 3 portion is to compare efficacy in subjects treated with ficerafusp alfa at the selected OBD plus Keytruda versus placebo plus Keytruda. Eligible subjects will be randomized 2:1 to the treatment group versus control group during phase 3.
“Supported by encouraging interim Phase 1/1b data, which demonstrated durable and clinically meaningful anti-tumor activity with ficerafusp alfa in combination with [Keytruda], FORTIFI-HN01 will evaluate the potential of ficerafusp alfa as a first-in-class treatment option for patients with advanced head and neck squamous cell carcinoma,” Dr. David Raben, Chief Medical Officer of Bicara Therapeutics, said in the news release. “The thoughtful and efficient design of this trial underscores our strategic approach to rapidly advancing treatment options for these patients, with the goal of addressing the significant unmet needs in this challenging disease.”
According to the release. HNSCC can arise from the mucosal epithelium of the oral cavity, pharynx and larynx, and are the most prevalent malignancies in the head and neck region. These cancers are common in the United States and globally, with incidence expected to rise to one million new cases annually by 2030. Around 10% of patients present with metastatic disease, and up to 30% experience recurrence or metastasis after initial treatment.
Furthermore, as per the release, most HNSCC cases are linked to mutations from carcinogenic exposures like tobacco smoke or HPV infection. Approximately 80% of recurrent or metastatic HNSCC cases are HPV-negative. These tumors often present with local recurrence and severe complications, including fatal tumor bleeding, pain, difficulty swallowing, significant weight loss and cachexia. This underscores the urgent need for therapies that provide durable anti-tumor effects and improve patients' quality of life.
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