ASP-1929 Photoimmunotherapy (PIT) Study in Patients With Recurrent Head/Neck Cancer

Inclusion Criteria:

• Provide written informed consent.

• Male or female ≥ 18 years of age at the time of informed consent

• Documentation of histologically confirmed, resectable (by standard of care surgery),primary or recurrent locoregional HNSCC or cuSCC.

Note: For patients with HNSCC, tumor locations must be in the oropharynx, oral cavity, sinonasal tract, hypopharynx, or larynx. Patients may not have a primary tumor site of nasopharynx (any histology).

• At least one tumor lesion accessible for ASP-1929 PIT illumination that is alsoamenable to imaging with the Fluorescence Imaging System camera (must be within 0.5cm and no more than 3 cm depth to the skin or mucosal surface, with the longestdiameter less than 5 cm as judged by pre-treatment imaging or examination) andradiographically measurable by RECIST 1.1, as assessed by the Investigator.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the timeof screening.

• Adequate organ function laboratory values (all screening labs should be performed ≤ 14 days of Day 1)

• Female patients of childbearing potential must not be pregnant (confirmed bynegative pregnancy test [urine or serum] at screening), not breastfeeding and mustbe willing to use a method of highly effective birth control, or practice abstinencethroughout the study and for 60 days after the last dose of ASP-1929.

• Male patients must be sterile or agree to use an adequate method of contraception orpractice abstinence throughout the study and for 60 days after the last dose ofASP-1929

• Provide fresh tumor biopsy at screening. Patients for whom a fresh screening biopsycannot be obtained may submit an archival sample provided it has been collectedwithin ≤ 3 months of enrollment and no intervening anticancer treatment has occurredwithin that timeframe or upon agreement from the Sponsor.

Exclusion Criteria:

• Receiving any other investigational agents or who have received local (includingradiotherapy) or systemic treatment for cancer (chemotherapy, immunotherapy, anysystemic investigational therapy, or EGFR-directed therapy) within 4 weeks beforeASP-1929 PIT treatment.

• History of significant (≥ Grade 3) infusion reaction to anti-EGFR antibodies.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to ASP-1929, or other agents used in study.

• Require use of photosensitizing medications. Note: Photosensitizing medications mustbe discontinued 30 days before ASP-1929 PIT treatment.

• Tumor invading major blood vessel unless the vessel has been embolized or surgicallyligated to prevent hemorrhage; must not have involvement of the common or internalcarotid arteries defined as invasion, encasement or direct contact (lack of aradiographically visible plane between the tumor and carotid artery).

• Tumors inappropriate for ASP-1929 PIT treatment, including those in the brain ordura, with perineural involvement at the skull base, CNS disease, or disease in theorbit (if the eye has been previously removed, consult with Medical Monitor beforeexcluding).

• History of distant metastatic disease (M1) based on standard of care imaging.

• Any contraindications for CT or 18FDG PET/CT imaging.

• Weight > 350 pounds (weight limit for scanner table), or unable to fit within theimaging gantry.

• Requiring future examinations or treatments within 4 weeks after an ASP-1929 PITtreatment cycle exposing the patient to high-intensity light (eg, eye examinations,surgical procedures) that are unrelated to ASP-1929 PIT treatment, the disease understudy, or the study overall.

• Diagnosed and/or treated for additional malignancy within 3 years before study Day 1, except for those with a negligible risk of metastasis or death

• Known history of testing positive for human immunodeficiency virus or acquiredimmunodeficiency syndrome -related illness.

• Known infection or detection of active Hepatitis B (eg, HBsAg positive), Hepatitis C (eg, RNA [qualitative]), or SARS-CoV-2 (qualitative).

• Received a live, attenuated vaccine within 4 weeks before Day 1 or anticipation ofreceiving a live, attenuated vaccine that will be required during the study (basedon known medical history).

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

• Major surgery or significant traumatic injury within 4 weeks of study Day 1, oranticipation of the need for major surgery that is unrelated to study interventionduring the study.

• Currently participating or has participated in a study of any investigational agentor used any investigational device within 4 weeks of study Day 1.

• Unwilling or unable to follow protocol requirements.

• Any other condition which, in the Investigator's opinion, deems the patient anunsuitable candidate to receive ASP-1929 and/or be exposed to illumination, mayaffect the interpretation of the results, or render the patient at high risk fromtreatment complications.

• Active infection requiring systemic therapies such as antibiotic, antifungal, orantiviral intervention which in the opinion of the Investigator precludes thepatient from participating in the clinical trial.