Efficacy and Safety Study of REM-001 Photodynamic Therapy for Treatment of Cutaneous Metastatic Breast Cancer (CMBC)

All participants must have stable or responding systemic disease for at least 3 months at screening.

REM-001 Therapy:

Day 1: REM-001 = 0.8 mg/kg (IV) at 2 mL/Kg/hr (over approximately 24 minutes)

Day 2: Light treatment per treatment area= 100 J/cm2 (10 min per treatment field) - 24 hrs (± 2 hrs) after infusion of REM-001.

Total area of target lesions treated will be < 200 cm2. Participants will be assessed at week 1, 4, 8, 12, 16, 20 and 24 weeks. An additional 4 weeks follow up will be undertaken if confirmatory assessment is required after week 24.

Assessments will include:

• cutaneous lesion response using photographic imaging
• area of ulceration using photographic imaging
• presence or absence of ulceration, bleeding, discharge and eschar
• patient-reported assessments for pain and itch, using numeric rating scales
• quality of life assessments
• safety On Day 1 of treatment, the participant will undergo an ECG assessment post-infusion and a blood sample for determination of concentration of REM-001 in plasma will be collected post-infusion.

Inclusion criteria

• Adult participants 18 years of age or greater.
• Participants able and willing to sign informed consent.
• Histopathologically confirmed breast cancer metastasis to the skin.
• Cutaneous metastasis not suitable for surgical resection.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Symptomatic lesions (including discomfort, pain, discharge, ulceration).
• Cutaneous, subcutaneous soft tissue, or superficial lymphatic metastasis that is amenable to PDT:

• Lesion(s) > 10 mm and < 60 mm in longest dimension.
• Lesion(s) exhibit at least one of the following symptoms: ulcerated, bleeding, discharging, itchy, painful.
• Judged by investigator as eligible for PDT.
• Participants are radiotherapy refractory (have received a radiation dose of 60 gray (Gy) or greater to the ipsilateral thorax) or are not otherwise amenable to radiotherapy.
• Disease progression on at least 2 courses of systemic therapy:

• HR positive/HER2 negative participants: should be refractory to endocrine therapy (at least 2 different regimens including at least one CDK4/6 inhibitor). Maintenance endocrine therapy at the clinician's discretion is allowed.
• HER2 positive participants should have had disease progression on at least 2 different regimens of HER2 targeted therapies. Maintenance therapy on trastuzumab (HERCEPTIN®) is allowed.
• If participants are on systemic therapy at enrollment, they must meet the following:

• Participants must have undergone a minimum of two cycles of systemic therapy prior to enrollment.
• The systemic therapy must be one from the Treatment of Physician's Choice (TPC) list, as follows: : eribulin mesylate (Halaven®); capecitabine (Xeloda®); Gemcitabine (Gemzar®); a taxane [either docetaxel (Taxotere®), nab-paclitaxel (Abraxane®), or paclitaxel (Taxol®)]; vinorelbine (Navelbine®); an antibody-drug conjugate [either sacituzumab-govitecan (Trodelvy®), trastuzumab-deruxtecan (Enhertu®), or ado-trastuzumab emtansine (KADCYLA®)]; pembrolizumab (Keytruda®); or carboplatin (Paraplatin®).
• Patients who are not on any chemotherapy will also be eligible.
• At the time of enrolment, participants should have no known plans to change or modify their TPC regimen while receiving study treatment. Note: TPC regimen may be changed or modified after treatment with REM-001 therapy, but this should be done in consultation with the Sponsor Medical Monitor.
• Adequate renal function, as evidenced by estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m2 using the CKD-EPI Creatinine Equation without race.
• Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, hemoglobin ≥ 8.5 g/dL and platelet count ≥ 100 × 10^9/L; INR < 1.5.
• Adequate liver function as evidenced by bilirubin ≤ 2.0 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × ULN (in the case of liver metastases ≤ 5 × ULN) [Participants with known Gilbert's Syndrome who have serum bilirubin < 1.5 x ULN (NCI CTCAE v5.0 Gr 2) may be enrolled].
• QTCF < 470msec on baseline ECG
• Woman of childbearing potential (WOCBP) must have a negative serum pregnancy test documented within 7 days prior to registration and must agree to practice adequate contraception
• Male patients must be sterile or willing to use an approved method of contraception from the time of treatment with REM-001 until 90 days after study drug treatment.

Exclusion criteria

• Participants who have received local cryotherapy, radiotherapy, intra-lesional chemotherapy, systemic or topical PDT, or surgery to study lesion fields within the past 12 weeks.
• Participants with progressive brain or subdural metastases, or leptomeningeal disease.
• Participants with previously treated brain or subdural metastases may participate provided:

• Previously treated brain metastases are stable and without evidence of progression, as determined by contrast-enhanced CT or MRI brain scan, for at least 4 weeks prior to the first dose of study treatment.
• There is no evidence of new brain metastases
• They have completed local therapy and discontinued the use of corticosteroids for this indication for at least 4 weeks prior to first dose of study treatment.
• Any neurologic symptoms attributed to brain metastases must have been stable for at least 4 weeks prior to study enrollment
• History of allergic or hypersensitivity reactions to light, egg proteins or egg yolk; history of porphyria, systemic lupus erythematosus, or xeroderma pigmentosum.
• Known disorder of lipoprotein metabolism or clearance (cholesterol> 400 mg/dl, and/or triglycerides > 500 mg/dl).
• Participants who have received investigational agents within the past 4 weeks or within 4 half-lives of the investigational agent (whichever is shorter) before the first study drug dose.
• Participants with inflammatory breast cancer.
• Known human immunodeficiency virus (HIV) infection with detectable virus titer.
• Active or chronic hepatitis B or C infection.
• Active or ongoing infection requiring systemic treatment.
• Participants who have undergone major surgery within 4 weeks of study treatment, or have planned surgery within 4 weeks of anticipated initiation of treatment with REM-001 therapy.
• Participants with otherwise unexplained weight loss (> 10% body weight) in the last 30 days prior to Screening.
• History of other malignancy treated with curative intent within the last 3-5 years. Exceptions are: Curatively treated basal cell/squamous cell skin cancer; carcinoma in situ of the cervix; superficial transitional cell bladder carcinoma
• Patients with other major or uncontrolled medical conditions, e.g., myocardial infarction or New York Heart Association (NYHA) Class III/IV heart failure within the last 6 months, stroke, uncontrolled diabetes, uncontrolled autoimmune disease.
• WOCBP that is pregnant or breast-feeding, or planning to become pregnant or breast-feed during protocol treatment and for 3 months after last dose of REM-001 therapy.
• WOCBP unwilling to use effective contraception during protocol treatment and for 3 months after last dose of REM-001 therapy.