Treatment With ASP-1929 Plus Anti-PD-1 Therapy Shows Promise in Advanced HNSCC

Ann M. Gillenwater, MD

Encouraging preliminary outcomes have been shown with ASP-1929 in combination with anti-PD-1 therapy in patients with locoregional/metastatic head and neck squamous cell carcinoma (HNSCC), according to a presentation given at the 11th International Conference on Head and Neck Cancer.¹

In 19 patients treated in cohort 1 of the phase 1b/2 study (ASP-1929-181; NCT04305795) investigating the use of photoimmunotherapy, ASP-1929 in combination with pembrolizumab (Keytruda) elicited an objective response rate (ORR) of 29.4% (95% CI, 10.3%-56.0%). Of the 5 patients who responded to treatment, 17.6% had a complete response and 11.8% had partial responses. At 18 months, the overall survival (OS) rate was 53.5% (95% CI, 18.5%-79.3%).

Results also showed that ASP-1929 plus anti-EGFR therapy was well-tolerated in the evaluated patient population. The study of ASP-1929 in recurrent or metastatic HNSCC is ongoing.

“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. 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, said Ann M. Gillenwater, MD, professor, Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, during the abstract presentation.

In the phase 1b/2 study, approximately 74 patients with advanced solid tumors, including those with HNSCC, will be assessed on study treatment. Cohort 1 will investigate the use of ASP-1929 administered intravenously on day 8 of every 6-week cycle plus pembrolizumab 200 mg given every 3 weeks on days 1 and 22 of each 6-week cycle in patients with first-line HNSCC. Patients in cohort 2 who have first-line locally advanced or metastatic SCC will be treated with ASP-1929 plus cemiplimab (Libtayo) 350 mg given every 3 weeks on days 1 and 22 of every 3-week cycle. In cohort 3, another group of patients with second-line locally advanced or metastatic cutaneous SCC will be administered ASP-1929 with cemiplimab. The doses and dosing schedule for cohort 3 are the same as cohort 2.²

The study is evaluating the coprimary end points of treatment-emergent adverse events (TEAEs) and serious TEAEs, and ORR in each cohort. The secondary end points of the study include OS, progression-free survival, and duration of response.

Patients are eligible for inclusion in either cohort of study given they have histologically or cytologically confirmed disease, a site of disease that is accessible to light illumination, measurable disease per modified RECIST v 1.1, an ECOG performance status of 0 or 1, and adequate organ function. Patients cannot be previously treated with systemic therapy in the recurrent/metastatic setting unless completed at least 6 months before the study as part of a multimodal regimen for locally advanced disease. All female patients are required to produce a negative pregnancy test, and all patients are required to use effective contraception during the study.

The study excludes individuals who have received prior anti-PD-1/anti-PD-L1 therapy from enrolling in cohorts 1 and 2. In addition, patients who previously received radiation therapy within 4 weeks prior to day 1 of the study, and who have not recovered completely from AEs are excluded. Receipt of prior allogeneic transplant and having had major surgery or a traumatic injury less within 28 days of day 1 of the study are also grounds for exclusion. Certain patients with an additional malignancy within 2 years before day 1 of the study, those a history of grade 3 or higher cetuximab (Erbitux) infusion reactions, known or active central nervous system involvement, active infection that requires systemic treatment, as well as other comorbidities that may interfere with study treatment, will also be excluded from the trial.

“We are truly honored to present the promising data from our ASP-1929-181 study at AHNS,” said Mickey Mikitani, co-chief executive officer of Rakuten Medical, in a press release.¹ “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, Inc. July 10, 2023. Accessed July 12, 2023. https://tinyurl.com/yempeptx}

_{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 12, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04305795}