A Phase 2a, Single-dose, Open-label Study to Evaluate Diagnostic Performance and Safety of Pegsitacianine, an Intraoperative Fluorescence Imaging Agent for the Detection of Cancer, in Patients With Unknown Primary Head and Neck Cancer (ILLUMINATE STUDY)

Inclusion Criteria:

1. Adults ≥18 years of age

2. Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinicalsuspicion in the opinion of the Investigator)

3. Part 1: Stage 1 to 4 HNSCC

4. Part 2: UPC squamous cell carcinoma of the head and neck with metastaticdisease to at least a single cervical node, AND no biopsy proven evidence ofthe primary cancer's location.

5. Acceptable hematologic status (as standard surgery protocol requires, as determinedby the Investigator), kidney function and liver function. Elevations of creatinine,alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or totalbilirubin >1.5× the upper limit of normal [ULN] must be determined to be notclinically significant by the Investigator and approved by the Medical Monitor.

6. Documented negative serum pregnancy test for women of childbearing potential (i.e.,premenopausal women with intact reproductive organs and women <2 years aftermenopause)

7. Male patients and female patients of child-bearing potential (i.e., premenopausalwomen with intact reproductive organs and women <2 years after menopause) must agreeto and comply with using medically acceptable contraception including surgicalsterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tuballigation), intrauterine device, oral contraceptive, contraceptive patch, long actinginjectable contraceptive, partner's vasectomy, double-barrier method (condom ordiaphragm plus spermicide or condom plus diaphragm), or abstinence during the trialand for 6 months thereafter

8. Agree to abstain from alcohol consumption from 72 hours before Pegsitacianineadministration through completion of Study Day 10 (±48 hours) visit in Part 1 andPart 2.

9. Adequate potential for follow up

Exclusion Criteria:

1. Tumors at sites of which the surgeon would assess that in vivo intraoperativeimaging would not be feasible.

2. Life expectancy <12 weeks

3. Karnofsky Performance Status <70%

4. Hepatic impairment (Child-Pugh score >5) or significant liver disease includingactive hepatitis or cirrhosis

5. Lab values or any sign, symptom, or medical condition that in the opinion of the PIwould prevent surgical resection

6. Medical or psychiatric conditions that compromise the patient's ability to giveinformed consent.

7. Pregnant or lactating women

8. Receiving or planned to receive, during the duration of the study, concomitantmedication with a high chance of hepatotoxicity, as judged by the PI based onstandard protocols within the study center

9. Alcohol consumption within 72 hours before Pegsitacianine administration

10. Received an investigational agent within the shorter of 5 half-lives or 30 daysbefore Pegsitacianine dosing

11. Inability to adhere to the schedule of assessments or any circumstance that wouldinterfere with the validity of assessments performed in the study

12. The PI considers that the patient should not participate in the study