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

Study Overview
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Brief Summary
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This is an open-label, single cohort study to confirm dose, assessments and timing of response, to support future studies. The primary objective of the trial is to evaluate cutaneous tumor response within total target treatment field to REM-001 therapy assessed using standardized digital photography

Detailed Description
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All participants will be receiving their Treatment of Physician's Choice for systemic disease and have stable disease for at least 12 weeks. REM-001 Therapy: Day 1: REM-001 = 0.8 mg/kg (IV) at 2 mL/Kg/hr (over34pprox.x. 25 min) 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.

Official Title
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An Open-Labeled, Single Arm Phase 2 Efficacy and Safety Study of REM-001 Photodynamic Therapy (PDT) for Treatment of Cutaneous Metastatic Breast Cancer (CMBC) That is Refractory or Not Eligible for Radiotherapy or Surgery

Conditions
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Cutaneous Breast Cancer

Intervention / Treatment
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* Combination Product: REM-001 photodynamic therapy


Participation Criteria
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Eligibility Criteria
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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.

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REM-001 photodynamic therapy (PDT)<br>Single arm study. All enrolled patients receive REM-001 therapy | Combination Product: REM-001 photodynamic therapy<br>* Infusion of REM-001 (iv) followed by light treatment to treatment field 24 hrs after infusion of REM-001<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Objective Response Rate (bORR) | Best Overall Objective Response Rate (bORR) [complete response (CR) or partial response (PR)] of target treatment fields at any time from treatment up to, and including, week 24. | Up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of best overall objective response | Duration of best overall objective response (CR or PR) based on initial target fields | Up to week 24 | 
| Time from baseline to the date of the first objective response (PR or CR) | Time from baseline to the date of the first objective response (PR or CR) | Up to week 24 | 
| Change from baseline in area of ulceration | How much the area of ulceration of initial target fields changes from that measured at baseline, when measured by standardized and calibrated digital photography. | Up to week 24 | 
| Change from baseline in area and volume of lesions | How much the area and volume of lesions of initial target fields changes from that measured at baseline when measured by the standardized and calibrated 3D digital photography | Up to week 24 | 
| Change from baseline in lesion discharge | Presence or absence of discharge of cutaneous lesion in initial target treatment field - investigator and independent review of photographs. | Up to week 24 | 
| Change from baseline in lesion bleeding | Presence or absence of bleeding of cutaneous lesion in initial target treatment field - investigator and independent review of photographs. | Up to week 24 | 
| Change from baseline in lesion eschar | Presence or absence of eschar of cutaneous lesion in initial target treatment field - investigator and independent review of photographs. | Up to week 24 | 
| Change from baseline in patient reported assessment of pain | Improvement or worsening of severity of pain using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire over 24 weeks from start of treatment | Up to week 24 | 
| Change from baseline in patient reported assessment of itch | Improvement or worsening of severity of itching using the Pruritus numerical rating scale (NRS) questionnaire over 24 weeks from start of treatment | Up to week 24 | 
| Change from baseline participant-reported overall quality of life | Improvement or worsening over 24 weeks from start of treatment in participant-reported overall quality of life assessed using the EORTC QLQ-C30 (v3.0) questionnaire | Up to week 24 | 
| Investigator-assessed objective response rate (ORR) | Investigator-assessed objective response rate (ORR) over of target treatment fields at any time from treatment up to and including week 24 | Up to week 24 | 
| Progression Free Survival (PFS) | Progression Free Survival (PFS) of systemic disease based on RECIST 1.1 | Up to week 24 | 
| Overall Survival (OS). | Overall Survival (OS). | Up to week 24 | 
| Adverse events | Incidence and severity of adverse events using CTCAE v5.0 until 24 weeks from treatment | Up to week 24 | 
| Safety assessments | Incidence and severity of clinically significant safety assessments: clinical laboratory examinations, vital signs, and physical exam | Up to week 24 | 
| Electrocardiogram (ECG) - QT interval | The effect of REM-001 therapy on QT interval post-infusion | Day 1 and 2 | 
| Plasma concentrations of REM-001 | Determination of plasma concentrations of REM-001 at the end of infusion (15 min post-infusion on day 1) and 24 hrs post-infusion prior to light treatment on day 2 | Day 1 and 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, cutaneous