ASP-1929 Plus Pembrolizumab Produces Responses, Proves Safe in Recurrent or Metastatic HNSCC

Ann M. Gillenwater, MD

Treatment with the antibody-dye conjugate ASP-1929 in combination with pembrolizumab (Keytruda) led to responses and was well tolerated in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to preliminary data from the phase 1b/2 ASP-1929-181 trial (NCT04305795).¹

Findings presented at the American Head and Neck Society’s (AHNS) 11th International Conference on Head and Neck Cancer showed that patients evaluable for efficacy (n = 17) experienced an overall response rate (ORR) of 29.4% (95% CI, 10.3%-56.0%), including a complete response rate of 17.6% and a partial response rate of 11.8%. Additionally, the 18-month overall survival (OS) rate was 53.5% (95% CI, 18.5%-79.3%).

Adverse effects were considered manageable.

“Patients with advanced head and neck cancer lack many treatment options and experience overall low survival and high locoregional recurrence. PD-1 therapy is used to treat various tumor types, including head and neck cancer,” Ann M. Gillenwater, MD, a professor in the Department of Head and Neck Surgery in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, said in a news release. “The preliminary results seen in this study warrant further study to evaluate its potential as a new innovative treatment for recurrent head and neck cancer. Targeting both EGFR-positive tumors and PD-1 blockade, the antitumor immune response is anticipated to result in improved tumor shrinkage that is durable compared to either monotherapy alone.”

ASP-1929 consists of the antibody cetuximab (Erbitux) and the light-activatable dye, IRDye^® 700DX. The agent is the first developed using Alluminox™, which is an investigational photoimmunotherapy platform. After binding to EGFR on cancer cells, illumination with 690 nm red light locally activates ASP-1929 to cause selective necrosis of cancer cells.

The open-label ASP-1929-181 trial is evaluating the combination of ASP-1929 and anti–PD-1 therapy in patients with EGFR-expressing solid tumors. The trial is including patients with histologically or cytologically confirmed recurrent locally and/or metastatic HNSCC with a combined positive score of at least 1 (cohort 1); patients with histologically or cytologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) not amenable to definitive surgery or radiation (cohort 2); and patients with histologically or cytologically confirmed locally advanced or metastatic CSCC not amendable to definitive surgery or radiation whose disease has progressed after at least 2 months of anti–PD-1 therapy.²

All patients must have at least 1 site of disease accessible to light illumination, have measurable disease per modified RECIST v1.1, and an ECOG performance status of 0 or 1. No prior systemic therapy in the recurrent or metastatic setting is allowed, unless it was completed at least 6 months prior to enrollment after being administered for the multimodal treatment of locally advanced disease.

Key exclusion criteria include prior anti–PD-1 or anti–PD-L1 therapy for patients in cohorts 1 and 2, radiation within 4 weeks of study treatment, prior allogeneic tissue or solid organ transplant, or known or active central nervous system metastases and/or carcinomatous meningitis.

In cohort 1, patients are receiving 200 mg of pembrolizumab on days 1 and 22 plus intravenous ASP-1929 on day 8 of each 6-week cycle for up to 24 months. Patients in cohorts 2 and 3 are being given the same regimen of ASP-1929 plus 350 mg of cemiplimab-rwlc (Libtayo) on days 1 and 22 of each 6-week cycle.

Determining the safety and tolerability of ASP-1929 plus anti–PD-1 therapy in the overall trial population is a primary end point, as well as tumor responses in the HNSCC and CSCC populations. Secondary end points include OS, progression-free survival, and duration of response.

“We are truly honored to present the promising data from our ASP-1929-181 study at AHNS,” Mickey Mikitani, co-chief executive officer of Rakuten Medical, said. “We are excited by the possibility that the addition of Alluminox treatment using ASP-1929 to standard of care anti–PD-1 therapy may provide meaningful progress in the treatment of head and neck cancer and potentially beyond.”

References

1. First safety and efficacy data of Rakuten Medical’s Alluminox treatment using ASP-1929 in combination with anti-PD-1 for recurrent and/or metastatic head and neck cancer presented at AHNS 2023. News release. Rakuten Medical. July 10, 2023. Accessed July 11, 2023. https://rakuten-med.com/us/news/press-releases/2023/07/10/7717/
2. An open-label study using ASP-1929 photoimmunotherapy in combination with anti-PD1 therapy in EGFR expressing advanced solid tumors. ClinicalTrials.gov. Updated January 11, 2023. Accessed July 11, 2023. https://clinicaltrials.gov/ct2/show/NCT04305795