A Study to Assess the Safety and Efficacy of UNO - Ultra High Concentration Nitric Oxide Injection in Combination With PD-1 Inhibitors Into Unresectable Solid Primary or Metastatic Tumors

This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of 2 parts: Phase 1a - a single treatment session, an evaluation period of 21±3 days, and safety and survival follow-up period of up to 12 weeks post-treatment, and Phase 1b - a single treatment session followed by PD-1 inhibitors treatment cycles, in PD-1 single agent progressors, to evaluate safety, overall response rate, duration of response, progression free survival, and overall survival follow-up until disease progression or death.

Inclusion Criteria: * Patient (male or female) is at least 18 years of age at the time of signature of the informed consent form. * Patient has an ECOG Performance Status score of 0-3 and with a life expectancy of ≥3 months. * Patient must have a confirmed diagnosis of at least one unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic solid tumor. Up to five target lesions may be identified. * No therapy of proven efficacy exists for the tumor, the tumor is not amenable to standard therapies, the tumor has failed to respond to standard therapy or has progressed despite standard therapy. * Patient has measurable disease on imaging based on RECIST Version 1.1. (non-measurable disease acceptable in Phase 1a) * Patient have adequate hematologic and organ function. * Patient have not had radiotherapy to the targeted lesions within the preceding 12 months. * Superficial tumor axis minimum length and depth of 4.5mm and must have a superficial region that can be fully traversed with a 32 mm-long needle with a 4.5 mm minimum depth. This criterion applies only for Phase 1a. . * Patient is not with childbearing potential or agrees to use adequate contraceptive methods Phase 1b specific Inclusion Criteria: * Tumor types include, but not limited to, metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC), unresectable or metastatic melanoma, high risk early-stage triple negative breast cancer or locally recurrent unresectable or metastatic breast cancer, and subjects with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC, basal cell carcinoma, merkel cell carcinoma, classical Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma (PMBCL), amendable to UNO administration, with cutaneous or subcutaneous lesions, will enroll to receive the combination therapy. * Superficial tumor axis of a 4.5 mm minimum length and depth; or accessible peripheral lymph node-based Investigator's judgement. * Previously received PD-1 directed immunotherapy and had either 1. Refractory to PD-1 2. Relapsed on single agent PD-1 3. Prolonged stable disease on single agent PD-1 ≥ 12 weeks Exclusion Criteria: * The tumor is situated in the lymph node (Phase 1a only), in thyroid, close to trachea or in facial area or other region which, in the Investigator's opinion, can pose extra risk to the patient. * The level of tumor vascularity was determined by the central radiologist, to pose a considerable risk for penetrating blood vessels during insertion of a 23G needle to the tumor. * Has received prior systemic anti-cancer therapy including investigational agents within 14 days of the start of study treatment. * Active central nervous system tumors or metastases.. * Received systemic corticosteroid therapy ≤1 week prior to study treatment or any other form of systemic immunosuppressive medication for medically significant acute or chronic conditions. * Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, neuropathy and protocol-defined laboratory values. * Active or prior documented autoimmune or inflammatory disorders - according to the discretion of the PI. * History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of enrolment. * Known active infection and uncontrolled intercurrent illness - according to the discretion of the PI. * Receiving drugs that have contraindication with NO. * Patient is receiving anticoagulants including low molecular weight heparin.