A Study to Find the Best Dose of ASP5354 to Show Lymph Nodes in People With Breast Cancer or Melanoma During Surgery

Study Overview
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Brief Summary
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This study is for women with breast cancer and for adults with melanoma. Breast cancer is a type of cancer when cells in the breast turn into cancer cells, which may grow out of control. Melanoma is a type of skin cancer that starts in cells called melanocytes. These cells make a substance called melanin which gives the skin its color. In this study, people will have surgery to remove the lymph node closest to the site of their cancer. This lymph node is called the sentinel node. This is done to check if the cancer has spread from the original site to the sentinel node. This procedure is called a sentinel node biopsy. This study will provide more information on a potential new dye, called ASP5354, used in sentinel node biopsies. ASP5354 may help to show the lymph nodes more clearly during surgery. This will help the surgeon find the lymph node closest to the site of the cancer (sentinel node). The main aim of the study is to find the best dose of ASP5354 that clearly shows the lymph nodes during surgery. This is an open-label study. That means each person in the study and the study doctors knew that person received ASP5354. Each person will only receive 1 dose of ASP5354. This dose will consist of 2 to 4 injections of ASP5354 around the cancer site. Small groups of people will each receive a different dose of ASP5354. The first group will receive a low dose of ASP5354. If the lymph nodes are clearly seen, the next group will receive a lower dose of ASP5354 and the following group will receive a dose of ASP5354 that is higher than the dose the first group received. Then, the results will be checked by an independent panel of experts. Depending on the results, the next groups may start on the current doses of ASP5354 or may receive a higher dose. In this study, up to 6 doses of ASP5354 may be given, but each person only receives 1 of these doses. People that want to take part in the study will be checked by a study doctor. This will be on a separate visit before their surgery. Before surgery, people who take part in the study will be asked if they have any other medical problems. They will have a physical exam, an ECG to check their heart rhythm, and have their vital signs checked (blood pressure, pulse rate, and breathing rate). Other checks will include some blood and urine samples taken for laboratory tests. During surgery, a study surgeon will inject ASP5354 near the cancer site. They will record how clearly they can see the lymph nodes. Some blood samples will be taken for laboratory tests and an ECG will be done. After their surgery, people will be asked if they have any other medical problems. People will return to the hospital 9 days later for a check-up. The check-up will include a physical exam, an ECG to check their heart rhythm, and a check of their vital signs (blood pressure, pulse rate, and breathing rate). Other checks will include some blood samples taken for laboratory tests. People will be asked if they have any medical problems and asked to complete a feedback survey.

Official Title
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A Phase 2 Open-label, Dose-finding Study to Determine the Optimal Dose for Lymph Node Visualization Using ASP5354 in Participants With Breast Cancer or Melanoma Undergoing Sentinel Lymph Node Biopsy

Conditions
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Sentinel Lymph Node Biopsy, Breast Cancer, Melanoma

Intervention / Treatment
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* Drug: pudexacianinium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has been diagnosed with localized breast cancer (female only, stage 1 to 2, N0 and M0) or melanoma (stage 1 to 2, N0 and M0) and is scheduled to undergo surgical intervention for systemic lymph node (SLN) detection and removal using Technetium-99m sulfur colloid or Lymphoseek as part of Standard of Care (SOC). Female participant is not pregnant and at least 1 of the following conditions apply: Not a woman of childbearing potential (WOCBP) WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final study treatment administration. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final study treatment administration. Female participant must not donate ova starting at first dose of Investigational Product (IP) and throughout the study period and for 30 days after final study treatment administration. Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use of contraception throughout the treatment period and for 30 days after final study treatment administration. Male participant must not donate sperm during the treatment period and for 30 days after final study treatment administration. Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final study treatment administration. Participant agrees not to participate in another interventional study while participating in the present study. Exclusion Criteria: Participant has had prior lymph node (LN) surgery in the area where LN detection is needed. Participant has had prior LN radiation in the area where LN detection is needed. Participant has had prior neo-adjuvant chemotherapy. Participant has definitive LN metastases. Participant has metastatic cancer. Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. Participant has any condition which makes the participant unsuitable for study participation. Participant has a known or suspected hypersensitivity to ASP5354, indocyanine green (ICG) or any components of the formulation used. Participant has had previous exposure to ASP5354. Participant has moderate to severe cardiac disease that limits daily functioning (New York Heart Association Class III-IV) or other medical conditions that would impact safety or study compliance. Participant has a resting heart rate <= 45 beats per minute (bpm) or >=115 bpm, systolic blood pressure >=160 mm Hg or diastolic blood pressure >= 100 mm Hg within 1 week prior to IP administration. If the blood pressure exceeds the limits above, repeat readings can be taken. Participant who has adequately controlled blood pressure is eligible. Participant has any of the screening laboratory values outside of the protocol specification criteria. Participant has received ICG, other near-infrared fluorescence (NIR-F) imaging agents, Blue dye (e.g., methylene blue or isosulfan blue) or magtrace within 2 weeks prior to IP administration. Participant has active alcohol abuse or illicit drug use (non-prescription or over-the-counter medications). Participant should not have consumed any alcohol or illicit drug (excluding cannabidiol products) within 24 hours of surgery.

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breast Cancer<br>Participants will receive a single dose of ASP5354. Up to 6 dose levels will be administered. | Drug: pudexacianinium chloride<br>* Subcutaneous or subareolar (breast cancer) or intradermal or peritumoral (melanoma)<br>* Other names: ASP5354;|
| Experimental: Melanoma<br>Participants will receive a single dose of ASP5354. Up to 5 dose levels will be administered. | Drug: pudexacianinium chloride<br>* Subcutaneous or subareolar (breast cancer) or intradermal or peritumoral (melanoma)<br>* Other names: ASP5354;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dose of ASP5354 for lymph node (LN) visualization | Optimal dose is defined as the dose that provides a better visualization compared to lower doses and a comparable visualization to the next higher dose. In case where 2 doses performed equally, lower dose would be selected. The optimal dose will be determined by the Visualization Review Committee (VRC) using data from the following assessments: LN tissue visualized (Y/N), visualized tissue is lymphatic in origin based on pathologic confirmation, Likert Scale determination of the intensity of fluorescence, and proportion of identified LN with histopathologic confirmation of LN tissue by ASP5354 compared with standard of care (SOC) treatment. | Up to end of surgery (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with at least 1 LN detected using ASP5354 | The visualization of at least 1 LN with histopathologic confirmation is assessed by using a binary Yes or No question. | Up to end of surgery (Day 1) | 
| Proportion of identified LN tissue by ASP5354 compared with Standard of Care (SOC) treatment | The proportion of identified LN with ASP5354 will be compared with SOC treatment with either Technetium-99m sulfur colloid (Tc-99mSC) or Lymphoseek, through histopathologic confirmation. | Up to end of surgery (Day 1) | 
| Number of participants with vital sign abnormalities and/or Adverse Events (AEs) | Number of participants with potentially clinically significant vital sign values | Up to 10 days | 
| Number of participants with electrocardiogram (ECG) abnormalities and/or AEs | Number of participants with potentially clinically significant ECG values | Up to 10 days | 
| Number of participants with laboratory value abnormalities and/or AEs | Number of participants with potentially clinically significant laboratory values. | Up to 10 days | 
| Number of participants with Treatment Emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study investigational product (IP), whether or not considered related to the study IP. A TEAE is defined as an AE observed after administration of the IP and up to the follow up period. | Up to 10 days | 
| Number of participants with serious adverse events (SAEs) | Adverse event (AE) is considered serious if the event: results in death, is life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, requires hospitalization or prolongation to hospitalization, or other medically important event. | Up to 10 days | 
| Pharmacokinetics (PK) of ASP5354 in plasma: concentration | Concentration will be recorded from the PK plasma samples collected. | Up to end of surgery (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP5354, pudexacianinium chloride, SLN, Breast Cancer, Melanoma