PHASE 3 RANDOMIZED CLINICAL TRIAL EVALUATING THE USE OF THE LASER-ASSISTED IMMUNOTHERAPY (LIT) SYSTEM IN ADVANCED BREAST CANCER

INTERVENTION: The Laser‐Assisted Immunotherapy treatment will be applied to palpable‐to‐touch laser‐accessible solid tumors ≥1 cm in diameter using an optical fiber inserted interstitially at the tumor site. The insertion of the interstitial laser fiber into the tumor will be accomplished by palpation of the tumor. The 805 nm diode laser parameters will be set at 3 W for 10 min. Within 1 h of laser treatment, a 1 mL dose of GC Injection will be injected in and around each laser‐treated area. The patients can receive up to 4 laser treatments per visit with a total GC Injection dose of 4 mL and total amount of laser exposure of 40 min. See detailed administration procedure in Section 7. Weekly oral administration of 100 mg/m2 Cyclophosphamide will be provided to patients in Arm 2 (LIT‐C), starting on Day 0 of the treatment schedule in each cycle (see Figure 1). For blinding purposes, patients in Arm 1 (LIT) will receive Placebo Cyclophosphamide treatment according to the same treatment schedule. The Control Arm study treatment will be up to the discretion of the treating physician, provided however, that all treatment decisions are within the Sponsor’s limitations. Such limitations include that patients in the Control arm will receive standard of care limited to standard radiation, hormone therapy, chemotherapy, and/or surgery. The drugs available in the Control Arm are: Capecitabine or hormone therapy. Both types of treatment will be provided by the Sponsor. Also the PI may select palliative treatment however this option needs to be discussed with the Medical Monitor prior to administration and the decision will need to be documented in the medical chart. CONDITION: ‐C509 Breast, unspecified ; Breast, unspecified Breast, unspecified PRIMARY OUTCOME: Intent‐to‐Treat (ITT) Analysis Set: Includes all enrolled patients who receive at least a partial dose of GC Injection. All safety analyses will be performed on this analysis set.; Efficacy and Immunology Analysis Set: Includes all patients in the ITT Analysis Set who have baseline values and at least 1 postbaseline value.; ; NAME OF THE RESULT: Analysis Populations; USED MEASURING METHOD :Patients will be assessed for changes in baseline for LIT only (Arm 1, LIT), LIT plus low‐dose cyclophosphamide (Arm 2, LIT‐C), and the control arm (Arm 3, Standard of Care), changes in nontreated tumors (local and metastatic), and presence of new measurable tumor lesions using irRC. Baseline descriptive statistics and changes from baseline statistics will be performed to evaluate overall tumor response based on irRC.; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 12 months SECONDARY OUTCOME: The extent of exposure will be summarized using descriptive statistics for number of patients treated per tumor type, number of tumors treated per visit and treatment cycle, number of treatment sites per tumor per visit and treatment cycle, total amount of GC Injection administered per visit and treatment cycle, total amount of exposure time to laser treatment per visit and treatment cycle, and total number of treatment visits administered in the treatment cycle ; NAME OF THE RESULT: Extent of Exposure ; USED MEASURING METHOD :irCR Inmuno response Criteria ; PERIOD OF TIME WHERE THE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE SECONDARY RESULT: 12 months INCLUSION CRITERIA: • Patient is ≥18 years of age. • Patient must have measurable disease. • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. • Patient has adequate organ function, confirmed by the following laboratory values obtained ≤14 days prior to the first treatment: o Bone Marrow Function:  Absolute neutrophil count (ANC) ≥1.5 × 109/L.  Platelets >75 × 109/L.  Hemoglobin ≥9 × 109/L. o Hepatic Function:  AST and ALT ≤3 × upper limit of normal (ULN); if liver metastases, then ≤5 × ULN.  Bilirubin ≤2.0 × ULN. o Renal Function:  Serum creatinine ≤2.0 × ULN or a creatinine clearance of >60 mL/min the calculation of the creatinine clearance will be performed using the cockcroft gault equation (CRCL). • Patient is willing to provide written informed consent and agrees to comply with visit schedule. •