Breakthrough Clinical Results
Rakuten Medical announced that it will present a Trial in Progress poster at the 2025 ASCO Annual Meeting, showcasing its global Phase 3 clinical trial (ASP-1929-381/ECLIPSE/NCT06699212) evaluating ASP-1929 photoimmunotherapy combined with pembrolizumab as a first-line treatment for recurrent head and neck squamous cell carcinoma (HNSCC). The poster will also highlight interim findings from the completed Phase 1b/2 study (ASP-1929-181/NCT04305795). The company also announced the expansion of patient enrollment to Taiwan, following the U.S., with Japan expected to follow soon. The Phase 3 trial will randomize 412 patients globally to receive either ASP-1929 plus pembrolizumab or the standard of care.
Key Highlights
- Phase 3 trial (ASP-1929-381) data to be presented at ASCO 2025.
- Trial enrollment expands to Taiwan, with Japan expected to follow.
- ASP-1929 photoimmunotherapy combined with pembrolizumab is being investigated as a first-line treatment for recurrent HNSCC.
- Interim data from the completed Phase 1b/2 study (ASP-1929-181) will also be presented.
Study Design Parameters
Study Design Parameters and Endpoints in Key HNSCC Trials
Study Design Parameters
A systematic review identified four phase III trials for anti-EGFR therapies in Head and Neck Squamous Cell Carcinoma (HNSCC). These trials involved three distinct patient populations: - Locally advanced HNSCC being treated for cure - Incurable advanced recurrent/metastatic HNSCC receiving first-line platinum-based chemotherapy - Incurable advanced recurrent/metastatic HNSCC with disease progression or unsuitable for platinum-based therapy
The EORTC HNCG-ROG 1219 DAHANCA trial included 169 patients treated with accelerated fractionated chemo-IMRT with/without hypoxic radiosensitizer Nimorazole for HNSCC.
One study investigated in vitro effects of combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on human HNSCC cell line, HSC-3.
A trial with 31 patients studied gefitinib administration 3 weeks before cisplatin/concurrent radiotherapy (CTRT), continued during CTRT, and for 4 months as consolidation.
The KEYNOTE-048 study was a pivotal clinical trial that investigated the efficacy of pembrolizumab (a monoclonal antibody) combined with chemotherapy as first-line therapy for recurrent or metastatic HNSCC. This study compared pembrolizumab-based therapy against the previous standard treatment of cetuximab + platinum-based therapy + 5-fluorouracil (the "EXTREME regimen").
Another phase III trial compared durvalumab (anti-PD-L1) or durvalumab plus tremelimumab (anti-CTLA-4) versus standard of care.
Key Trial Endpoints
Primary Endpoints
- Overall survival (OS) was a primary outcome in multiple trials
- Progression-free survival (PFS) was another key primary endpoint
- The phase III trial of oral metronomic chemotherapy versus intravenous cisplatin used median overall survival as its primary endpoint with a non-inferiority margin of 13%
- In the durvalumab trial, primary endpoints were OS for durvalumab versus standard of care, and OS for durvalumab plus tremelimumab versus standard of care
Secondary Endpoints
- Quality of life
- Tumor response rate and duration
- Toxicity associated with anti-EGFR therapies
- Objective response rate
- Duration of response
- In DAHANCA trials evaluating p16 expression: Loco-regional control (LRC), event-free survival (EFS), and overall survival
Biomarkers and Other Outcomes
- Biomarkers measured in some trials included EGFR protein expression, FISH, mutational status, and MMP11 protein expression
- Grade 3 oral mucositis (g3OM) was validated using the EORTC HNCG-ROG 1219 DAHANCA trial dataset
- In the gefitinib trial: median disease-free survival 1.3 years, median survival time 2.4 years, 3-year disease-free survival 42.9%, and 3-year overall survival 48.4%
- Early phase trials of tgDCC-E1A gene therapy included endpoints related to dosing and safety, levels of gene transfer, tumor response, and downregulation of HER-2/neu expression
Statistical methods included external validity assessment using the scaled Brier score, calibration with calibration curves, and discrimination calculated using the area under the receiver operating curve (AUC-ROC).
Incidence and Prevalence
Global Incidence and Prevalence of Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) represents a significant global health burden, ranking as the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. Approximately 90-90% of all head and neck cancers are represented by squamous cell carcinoma (SCC).
According to the GLOBOCAN 2020 database, which provides estimates of incidence and mortality rates for six types of head and neck cancer, the global burden of this disease continues to evolve in complex patterns.
Regional Distribution
The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. In the United States, head and neck cancer accounts for approximately 2% of all cancers and 2% of cancer deaths. A total of 75,000 cases of head and neck cancer were diagnosed in 2001 in the United States, with 30,000 deaths in the same year.
Changing Trends
Despite falls in alcohol consumption and a reduction in smoking, the incidence rate of new disease continues to rise. This trend varies significantly by anatomical site:
Increasing Incidence Sites:
- Thyroid (up 52%)
- Bone (43%)
- Soft tissues (20%)
- Salivary (20%)
- Tongue (16%)
- Tonsil (12%)
- Nose (12%)
Decreasing Incidence Sites:
- Lip (down 58%)
- Hypopharynx (35%)
- Cervical esophagus (32%)
- Oropharyngeal mucosa (26%)
- Larynx (26%)
HPV-Related Cases
The incidence of HPV-related oral squamous cell carcinoma (OSCC) appears to be on the rise, while HPV-unrelated OSCC tends to have stabilized in the past decades.
Mortality Trends
Mortality has decreased to some degree at all sites except thyroid where it was stable. However, oral squamous cell carcinoma (OSCC) is still associated with a high death rate of around 50% in some regions of the world.
This evolving epidemiological landscape highlights the importance of targeted prevention strategies, early detection, and continued research into effective treatments for head and neck squamous cell carcinoma.
Drug used in other indications
Based on the provided context, there is no information available about ASP-1929 and pembrolizumab being trialed for indications other than Head and neck squamous cell carcinoma. The context does not contain any data about ASP-1929 at all. While pembrolizumab is mentioned in relation to head and neck squamous cell carcinoma (HNSCC), there is no information about its use with ASP-1929 for other indications.
Similarly, there is no information in the provided context about intervention models for trials involving ASP-1929 and pembrolizumab for any indications other than HNSCC.
The context contains information about various other clinical trials for head and neck cancer treatments, including: - A randomized controlled trial investigating swallowing and mouth-opening exercises combined with progressive resistance training (PRT) during radiotherapy - The LUX-Head & Neck 1 study evaluating afatinib versus methotrexate in R/M HNSCC patients - The GATTO study (NCT03360734) exploring the combination of gatipotuzumab with tomuzotuximab or commercial anti-EGFR antibody - A phase I trial evaluating cetuximab plus cabozantinib in patients with recurrent/metastatic HNSCC
However, none of these trials involve ASP-1929 and pembrolizumab.