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)

Study Overview
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Brief Summary
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This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent.

Detailed Description
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This is a non-randomized, open-label, single-center, safety and imaging feasibility study of Pegsitacianine, an intraoperative fluorescence imaging agent. The main purpose of this study is to investigate whether Pegsitacianine can be used to image head and neck cancers as well as unknown primary cancer of the head and neck 6-100 hours post dose in patients undergoing routine surgery for biopsy, evaluation, detection or removal of their primary cancer. The study consists of two Parts. Part 1 will be performed in a single dose of 1 mg/kg given such that Pegsitacianine fluorescence can be used to image primary tumors in patients with HNSCC undergoing routine surgery at 6-100 hours, and if needed at an alternate imaging schedule post dose. Part 2 will be performed in a single dose of 1 mg/kg given such that Pegsitacianine fluorescence can be used to image primary tumors in patients with unknown primary cancer of the head and neck (UPC) at 6-100 hours, and if needed at an alternate imaging schedule post dose.

Official Title
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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)

Conditions
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Head and Neck Cancer, Unknown Primary Cancer, Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Pegsitacianine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 years of age Biopsy-confirmed diagnosis, for primary or recurrent disease (or high clinical suspicion in the opinion of the Investigator) Part 1: Stage 1 to 4 HNSCC Part 2: UPC squamous cell carcinoma of the head and neck with metastatic disease to at least a single cervical node, AND no biopsy proven evidence of the primary cancer's location. Acceptable hematologic status (as standard surgery protocol requires, as determined by the Investigator), kidney function and liver function. Elevations of creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or total bilirubin >1.5× the upper limit of normal [ULN] must be determined to be not clinically significant by the Investigator and approved by the Medical Monitor. Documented negative serum pregnancy test for women of childbearing potential (i.e., premenopausal women with intact reproductive organs and women <2 years after menopause) Male patients and female patients of child-bearing potential (i.e., premenopausal women with intact reproductive organs and women <2 years after menopause) must agree to and comply with using medically acceptable contraception including surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation), intrauterine device, oral contraceptive, contraceptive patch, long acting injectable contraceptive, partner's vasectomy, double-barrier method (condom or diaphragm plus spermicide or condom plus diaphragm), or abstinence during the trial and for 6 months thereafter Agree to abstain from alcohol consumption from 72 hours before Pegsitacianine administration through completion of Study Day 10 (±48 hours) visit in Part 1 and Part 2. Adequate potential for follow up Exclusion Criteria: Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible. Life expectancy <12 weeks Karnofsky Performance Status <70% Hepatic impairment (Child-Pugh score >5) or significant liver disease including active hepatitis or cirrhosis Lab values or any sign, symptom, or medical condition that in the opinion of the PI would prevent surgical resection Medical or psychiatric conditions that compromise the patient's ability to give informed consent. Pregnant or lactating women Receiving or planned to receive, during the duration of the study, concomitant medication with a high chance of hepatotoxicity, as judged by the PI based on standard protocols within the study center Alcohol consumption within 72 hours before Pegsitacianine administration Received an investigational agent within the shorter of 5 half-lives or 30 days before Pegsitacianine dosing Inability to adhere to the schedule of assessments or any circumstance that would interfere with the validity of assessments performed in the study The PI considers that the patient should not participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In Part 1 the single dose of 1 mg/kg of pegsitacianine given 6-100 hours prior to surgery will be used to image primary tumors in patients with HNSCC to evaluated to verify the diagnostic performance of pegsitacianine fluorescence imaging for detecting primary tumors and metastatic lymph nodes. In Part 2, pegsitacianine the single dose of 1 mg/kg of given 6-100 hours prior to surgery will be used to in patients with unknown primary cancer of the head and neck. These patients typically undergo exam under anesthesia with a laryngoscopy as well as panendoscopy for identifying the source of the metastatic cancer found in the cervical nodes. Subjects for Part 2 may begin dosing at any time during Part 1 thus the two parts can run concurrently.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part 1 - Cohort A<br>In Part 1 the single dose of 1 mg/kg of pegsitacianine given 6-100 hours prior to surgery will be used to image primary tumors in patients with HNSCC to evaluated to verify the diagnostic performance of pegsitacianine fluorescence imaging for detecting primary tumors and metastatic lymph nodes. | Drug: Pegsitacianine<br>* Infusion of the Pegsitacianine-Intraoperative fluorescence imaging<br>|
| Active Comparator: Part 2 - Cohort B<br>In Part 2, pegsitacianine the single dose of 1 mg/kg of given 6-100 hours prior to surgery will be used to in patients with unknown primary cancer of the head and neck. These patients typically undergo exam under anesthesia with a laryngoscopy as well as panendoscopy for identifying the source of the metastatic cancer found in the cervical nodes. The diagnostic performance of pegsitacianine fluorescence imaging for detecting primary tumors and metastatic lymph nodes in these patients will be evaluated. All the available data to date will be used to decide the additional tumor type(s), number of patients per tumor type, and number of Group(s) to be enrolled. | Drug: Pegsitacianine<br>* Infusion of the Pegsitacianine-Intraoperative fluorescence imaging<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostics performance and safety of 1 mg/kg Pegsitacianine in patients with HNSCC | Pegsitacianine fluorescence from in vivo and excised tissues will be imaged using intraoperative and post-operative NIR cameras and will be correlated with the histopathological confirmation of tumor and normal tissues to determine Pegsitacianine's diagnostic performance. Patient safety will be assessed for 10 days (±48 hours) post dose. All patients will be monitored for vital signs and physical examination pretreatment and at various time points up to Day 6 (±24 hours). All patients will be monitored for comprehensive metabolic panel (CMP) and complete blood count (CBC) with differentials pretreatment and at various time points up to Day 10 (±48 hours). All patients will be monitored for TEAEs, and concomitant medication use from the start of dosing up to Day 10 (±48 hours). TEAEs will be followed closely during the study to identify any potential DLTs | 5 years | 
| Diagnostics performance and safety of 1 mg/kg Pegsitacianine in patients with UPC | Pegsitacianine fluorescence from in vivo and excised tissues will be imaged using intraoperative and post-operative NIR cameras and will be correlated with the histopathological confirmation of tumor and normal tissues to determine Pegsitacianine's diagnostic performance. Patient safety will be assessed for 10 days (±48 hours). All patients will be monitored for vital signs and physical examination pretreatment and at various time points up to Day 6 (±48 hours). All patients will be monitored for comprehensive metabolic panel (CMP) and complete blood count (CBC) with differentials pretreatment and at various time points up to Day 10 (±48 hours). All patients will be monitored for TEAEs, and concomitant medication use from the start of dosing up to Day 10 (±48 hours). TEAEs will be followed closely during the study to identify any potential DLTs | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pegsitacianine fluorescence imaging in HNSCC, UPC primary cancers that are HPV positive and HPV negative | Pegsitacianine fluorescence from in vivo and excised tissues will be imaged using intraoperative and post-operative NIR cameras and will be correlated with the histopathological confirmation of tumor and normal tissues to determine Pegsitacianine's diagnostic performance. Assessment of use of Pegsitacianine for intra-operative imaging of HNSCC, UPC and metastatic lymph nodes will include quantification of intraoperative and postoperative fluorescence signals from histology confirmed tumor and normal tissues, calculation of TBR and diagnostic performance. Feasibility determination will be based on a combined assessment of intraoperative in vivo and ex vivo fluorescent signals together with ex vivo examinations (histological examination, NIR flatbed scanning). | 5 years |