Rakuten Medical has commenced a global, multi-regional Phase 3 clinical trial (ASP-1929-381, also known as ECLIPSE) to investigate the efficacy and safety of ASP-1929 photoimmunotherapy in combination with pembrolizumab (Keytruda) as a first-line treatment for locoregional recurrent head and neck squamous cell carcinoma (HNSCC) without distant metastases. The first patient was dosed at the Avera Cancer Institute in Sioux Falls, South Dakota.
The trial, registered as NCT06699212, is a randomized, open-label study designed to enroll approximately 400 patients across sites in the United States, Japan, and Taiwan, with plans for further expansion to additional countries. Participants will be randomized to either the experimental arm, receiving ASP-1929 photoimmunotherapy in conjunction with pembrolizumab, or the control arm, receiving the current pembrolizumab-based standard of care, which may include pembrolizumab alone or in combination with chemotherapy, at the physician's discretion.
The primary endpoint of the study is overall survival (OS). Key secondary endpoints include complete response rate (CRR) and overall response rate (ORR).
Rationale Behind the Combination Therapy
The rationale for combining ASP-1929 photoimmunotherapy with pembrolizumab stems from the unique mechanism of action of each therapy. Photoimmunotherapy involves a biophysical disruption of targeted cells, while pembrolizumab, an anti-PD-1 antibody, has become a mainstay in systemic treatment for recurrent/metastatic HNSCC. The trial aims to determine whether the combination of ASP-1929 and pembrolizumab can produce synergistic antitumor effects, potentially improving outcomes for patients with locoregional recurrent HNSCC.
Prior Clinical Data
The Phase 3 trial is informed by data from an interim evaluation of 19 patients enrolled in the HNSCC cohort of a prior Phase 1b/2 study (ASP-1929-181, NCT04305795). This data, with a cut-off of August 31, 2023, showed an estimated 24-month survival rate of 52.4%, with a median OS not yet reached, and a generally tolerated safety profile.
Disease Burden and Unmet Need
Head and neck cancer is the 7th most common cancer globally, with over 90% classified as squamous cell carcinoma. More than 60% of HNSCC patients present with locally or regionally advanced disease (stage III or IV), and 15-40% of these patients will experience recurrence. Recurrent HNSCC carries a poor prognosis, with a 5-year overall survival rate of less than 50%.
About ASP-1929
ASP-1929 is an antibody-dye conjugate comprised of cetuximab and IRDye 700DX, a light-activatable dye. It binds to epidermal growth factor receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors. 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, leading to selective necrosis of cancer cells. In Japan, ASP-1929 received marketing approval for unresectable locally advanced or recurrent head and neck cancer in September 2020.
Expert Commentary
Dr. Kristen Coffroth, MD of Avera Medical Group Ear, Nose & Throat - Head and Neck Surgery, and an investigator for the trial, stated, "Photoimmunotherapy has a unique mode of action, which involves a biophysical disruption of targeted cells. Pembrolizumab has become a mainstay in systemic treatment for recurrent/metastatic HNSCC. This trial will evaluate whether the combination of ASP-1929 photoimmunotherapy with pembrolizumab can harness synergistic antitumor effects, which may shed new light on the treatment of locoregional recurrent HNSCC."
Dr. William Chad Spanos, MD, FACS, Principal Investigator for the study at the Avera Cancer Institute, added, "I am impressed by the technology behind photoimmunotherapy, which offers a novel and targeted approach to cancer treatment. Combining this with pembrolizumab has the potential to expand first-line treatment options for patients with recurrent HNSCC."
Mickey Mikitani, CEO of Rakuten Medical, expressed optimism about the potential of the combination therapy to improve treatment outcomes in recurrent head and neck cancer, citing encouraging data from the Phase 1b/2 study.
