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

This is an interventional treatment trial for Cutaneous Breast Cancer focused on measuring metastatic, cutaneous Read More

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). They may reinstate maintenance endocrine therapy at the clinician's discretion when they are not receiving TPC chemotherapy.
  • HER2 positive participants should have had disease progression on trastuzumab (HERCEPTIN®) +/- pertuzumab (PERJETA™) and ado-trastuzumab emtansine (KADCYLA®)) treatment regimens. Maintenance therapy on trastuzumab (HERCEPTIN®) is allowed.
• Participants must be receiving one of the following Treatments of Physician's Choice (TPC) for at least 3 months at screening: eribulin mesylate (Halaven®); capecitabine (Xeloda®); Gemcitabine (Gemzar®); a taxane [either docetaxel (Taxotere®), nab-paclitaxel (Abraxane®), or paclitaxel (Taxol®)]; or vinorelbine (Navelbine®); or an antibody-drug conjugate [either sacitiuzumab-govitecan (Trodevly®) or trastuzumab-deruxtecan (Enhertu®)]
• Patients with stable or responding systemic disease (as determined by at least 2 consecutive assessments at 6-week intervals) can continue to receive the same therapy (TPC) during treatment.
• 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.