- Combination therapy showed promising initial efficacy with a median OS of 25.6 months and a preliminary manageable safety profile in recurrent/metastatic HNSCC
- Global Phase 3 trial of the combination therapy is underway to further evaluate efficacy and safety as a first-line treatment for recurrent HNSCC
San Diego, CA — Rakuten Medical, Inc., a global biotechnology company developing and commercializing Alluminox™ platform-based photoimmunotherapy, today announced the publication of results from a Phase 1b/2 clinical study of ASP-1929 photoimmunotherapy in combination with pembrolizumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in the peer-reviewed journal Head & Neck.
The article presents updated interim evaluation results (data cut-off: April 30, 2024) from 19 patients enrolled in the HNSCC cohort of the open label ASP-1929-181 trial (ClinicalTrials.gov Identifier: NCT04305795). Findings showed early efficacy signals, particulary overall survival (OS), and tolerability. In addition, exploratory biomarker analyses suggested that ASP-1929 photoimmunotherapy plus pembrolizumab may increase anti-tumor immunity at the targeted lesion.
Title: Safety and Efficacy Findings From a Phase Ib/II Study of ASP-1929 Photoimmunotherapy With Pembrolizumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
DOI: https://doi.org/10.1002/hed.70014
Key Findings (data cut-off: April 30, 2024):
Efficacy (N=18*):
- Median OS: 25.6 months (95% CI, 14.6–NE)
- Objective response rate (ORR): 27.8% (95% CI, 9.7–53.5), including 22.2% (95% CI, 6.4–6) confirmed complete response (CR)
- Disease control rate (DCR): 61.1% (95% CI, 35.7–82.7)
- Median time to response: 1.4 months; most responses observed after 1st cycle of treatment
- All CRs exceeding 16 months and ongoing at data cutoff
* 18 out of 19 patients received a minimum of one complete treatment with both pembrolizumab and ASP-1929 photoimmunotherapy.
Safety (N=19):
- All patients experienced > 1 treatment-emergent adverse event (TEAE)
- Most common TEAEs: fatigue (57.9%), oral pain (52.6%), constipation (36.8%)
- Serious TEAEs observed in 63.2% of patients, most commonly dysphagia and tongue edema (2 patients 10.5% each)
- No fatal treatment-related AEs; overall safety profile consistent with prior ASP-1929 photoimmunotherapy and pembrolizumab experiences
Exploratory Biomarker Analyses:
- Tumor biopsies showed an increase in CD8+ T-cell densities and reduction of EGFR expression in treated lesions
- B-cell proliferation and activation in responders further suggested a modification of the tumor microenvironment toward antitumor immunity
“These early results are encouraging for patients with recurrent or metastatic head and neck squamous cell carcinoma, a population with very limited treatment options,” said David M. Cognetti, The Herbert Kean, MD Professor and Chair, Department of Otolaryngology – Head and Neck Surgery at Thomas Jefferson University and lead author of the study. “In this preliminary evaluation, the combination of ASP-1929 photoimmunotherapy and pembrolizumab showed not only durable responses but also a median overall survival of more than two years, highlighting the potential of this novel approach when standard therapies are no longer viable.”
Based on the results, Rakuten Medical has initiated a global Phase 3 ASP-1929-381 trial (ClinicalTrials.gov Identifier: NCT06699212) to further evaluate ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line therapy for recurrent HNSCC. Currently, over 15 clinical sites across the United States, Taiwan, and Japan are actively recruiting patients, with additional sites expected in these regions. To further accelerate enrollment, the trial will also expand to Eastern Europe, including new sites in Ukraine and Poland. Following completion of the Phase 3 trial, Rakuten Medical will evaluate the potential to submit a Biologics License Application (BLA) for ASP-1929 in the United States as early as 2028.
About ASP-1929-181 Study
The ASP-1929-181 study is an open label 1b/2 trial of ASP-1929 photoimmunotherapy with pembrolizumab in patients with EGFR-expressing advanced solid tumors. The trial included a subprotocol for the treatment of patients with recurrent locally advanced or metastatic HNSCC, which is the subject of this manuscript.
About ASP-1929-381 Study
The ASP-1929-381 study is a multi-regional, multi-center, randomized, open-label Phase 3 trial, designed to assess the efficacy and safety of ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line treatment for locoregional recurrent HNSCC without distant metastases. 412 patients globally will be randomized to either an experimental arm receiving ASP-1929 photoimmunotherapy in combination with pembrolizumab, or a control arm receiving the current pembrolizumab-based standard of care (SOC), where patients may receive pembrolizumab alone or in combination with chemotherapy according to the physician's choice. The primary endpoint is Overall Survival (OS), with key secondary endpoints including Complete Response Rate (CRR) and Overall Response Rate (ORR).
About Rakuten Medical, Inc.
Rakuten Medical, Inc. is a global biotechnology company developing and commercializing Alluminox™ platform-based photoimmunotherapy, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing. Rakuten Medical’s photoimmunotherapy is currently investigational outside Japan. Rakuten Medical is committed to its mission to conquer cancer by developing its pioneering treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries/regions, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit www.rakuten-med.com.
About Alluminox™ platform
The Alluminox™ platform is Rakuten Medical’s investigational technology platform that combines pharmaceuticals, medical devices, medical technology, and other peripheral technologies. Rakuten Medical is developing Alluminox platform-based photoimmunotherapy, which involves two key steps: 1) drug administration and 2) targeted illumination using medical devices. The drug component consists of a cell-targeting moiety conjugated to a light-activatable dye, such as IRDye® 700DX (IR700), that selectively binds to the surface of targeted cells, such as tumor cells. The device component consists of a light source that locally illuminates the targeted cells with red light (690nm) to transiently activate the drug. Rakuten Medical’s pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted tumor cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Photoimmunotherapy was originally developed by Dr. Hisataka Kobayashi and his team at the National Cancer Institute in the United States. Outside Japan, Rakuten Medical’s Alluminox platform-based photoimmunotherapy is investigational.
About ASP-1929
Rakuten Medical’s first pipeline drug developed on its Alluminox™ platform is ASP-1929, an antibody-dye conjugate comprised of the anti- epidermal growth factor receptor (EGFR) antibody cetuximab and IRDye® 700DX, a light activatable dye. ASP-1929 binds to EGFR, a cancer antigen expressed in multiple types of solid tumors, including head and neck, breast, lung, colorectal, prostate and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by illumination with red light (690 nm), emitted by a laser device system to produce a photochemical reaction. This reaction is believed to cause damage to the membrane of cancer cells, leading to selective necrosis of cancer cells. In Japan, ASP-1929 received marketing approval from the Japanese Ministry of Health, Labor, and Welfare for unresectable locally advanced or recurrent head and neck cancer in September 2020, under the Sakigake Designation System and the Conditional Early Approval System. ASP-1929 photoimmunotherapy in combination with pembrolizumab is currently under investigation in a global Phase 3 clinical trial as a first-line therapy for recurrent head and neck cancer. Outside Japan, ASP-1929 has not yet been approved for commercial use by any regulatory authority.
