New Trial to Test Light Therapy Plus Keytruda in Head and Neck Cancer

ASP-1929 photoimmunotherapy plus Keytruda is being evaluated in HNSCC.

Investigators are launching a global multi-regional phase 3 clinical trial that is to evaluate ASP-1929 photoimmunotherapy in combination with Keytruda (pembrolizumab) as a first-line therapy in patients with recurrent head and neck squamous cell carcinoma (HNSCC), according to a news release from Rakuten Medical announced.

Furthermore, the first patient enrolled onto the trial recently received a study treatment at the Avera Cancer Institute in Sioux Falls, South Dakota. Patient enrollment is also planned for sites in Japan and Taiwan, with further expansion planned to other countries and regions.

"Photoimmunotherapy has a unique mode of action, which involves a biophysical disruption of targeted cells. [Keytruda] has become a mainstay in systemic treatment for recurrent/metastatic HNSCC,” Dr. Kristen Coffroth an expert in Head and Neck Surgery, Ear, Nose & Throat and Otolaryngology, at Avera Medical Group, and one of the investigators for the ASP-1929-381 study at the Avera Cancer Institute, stated in the news release. “This trial will evaluate whether the combination of ASP-1929 photoimmunotherapy with [Keytruda] can harness synergistic antitumor effects, which may shed new light on the treatment of locoregional recurrent HNSCC."

This study builds on interim evaluation data from 19 patients enrolled in the HNSCC cohort of a prior phase 1b/2 study, ASP-1929-181. The data indicated an estimated 24-month survival rate of 52.4%, with a generally tolerated safety and a median overall survival (OS) that was not reached. Specifically, there were no fatal serious side effects nor synergistic serious side effects reported due to ASP-1929 and anti-PD-1, though two life-threatening serious side effects were noted.

The phase 3 trial is evaluating ASP-1929 photoimmunotherapy plus anti-PD-1 Keytruda as a first-line treatment for recurrent, locoregional HNSCC without distant spreading of the disease. The randomized, open-label study will enroll approximately 400 patients globally, assigned to either the experimental treatment group, consisting of ASP-1929 photoimmunotherapy plus Keytruda, or the control therapy group, evaluating the Keytruda-based standard of care, which may include chemotherapy.

Patients will be enrolled onto the study and across three treatment groups: ASP-1929 PIT at doses of 320 milligrams per square meter (mg/m²) or 640 mg/m² combined with Keytruda, or a standard-of-care group where patients may receive Keytruda alone or Keytruda plus chemotherapy by a physician's choice.

The primary end goal of the study is OS, while secondary end goals include complete response rate and overall response rate.

According to the news release, ASP-1929 is an antibody-dye conjugate that binds to epidermal growth factor receptor (EGFR), a cancer antigen expressed in various solid tumors. After binding to cancer cells, ASP-1929 is activated by red light, causing damage to the cancer cell membrane and selective necrosis. In Japan, ASP-1929 received marketing approval for unresectable locally advanced or recurrent head and neck cancer in 2020. Outside Japan, it hasn’t been approved by any regulatory authority.

Dr. William Chad Spanos, an expert in Ear, Nose & Throat and Head and Neck Surgery, as well as the Principal Investigator for the ASP-1929-381 study at the Avera Cancer Institute, emphasized that he is, “…impressed by the technology behind photoimmunotherapy, which offers a novel and targeted approach to cancer treatment. Combining this with [Keytruda] has the potential to expand first-line treatment options for patients with recurrent HNSCC. I am pleased to initiate this groundbreaking trial at our site and look forward to contributing to advancing care for patients facing this challenging disease."