Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including Mesothelioma

Inclusion Criteria:

1. Male or female ≥ 18 years old.
2. ECOG performance status 0-1.
3. Histological diagnosis of solid tumor/mesothelioma with MPE. Expansion Cohort 2:
4. only patients with breast cancer, ovarian cancer or non-small cell lung cancer.
5. patients for whom paclitaxel is a recommended SoC therapy.
6. no contraindications to paclitaxel.
7. Patients with a disease burden that is predominantly pleural, and a pleural space thatis accessible. Expansion Cohorts 1 and 2: MPE (non-mesothelioma): patients must have received at least 1prior standard of care treatment regimen for advanced, unresectable malignancy, withdocumented progression. Expansion Cohort 3: MPE mesothelioma: patients must have received at least 1 prior standard-of-care treatmentregimen for advanced, unresectable malignancy, with documented progression and there is noapproved life extending alternative available. Expansion Cohort 4: MPE mesothelioma 'window of opportunity': patients should be treatmentnaïve, have refused or not be immediately requiring of systemic therapy and should bepatients for whom drainage is planned immediately while further treatment options arearranged. It must be documented for each patient that protocol participation will notaffect their subsequent ability to access standard systemic first line therapy due toRSO-021 being a local therapy.
8. Resolution of all acute reversible toxic effects of prior therapy or surgical procedureto Grade ≤1 (except alopecia).
9. For dose escalation: Archival paraffin block, ideally from the patient's most recentbiopsy, should be provided prior to the first dose of study therapy, if sufficient tissueis available. For dose expansion cohorts: fresh tumor biopsy must be obtained.
10. Patients enrolled in the mesothelioma expansion phase will be requested to undergo atumor biopsy during the screening period and after the third dose.
11. Patients enrolled in the non-mesothelioma expansion phase will be requested to undergoa tumor biopsy during the screening period and after the third dose only if medicallyfeasible.
12. Patients must have adequate organ function.

Exclusion Criteria:

1. Last dose of prior anti-cancer therapies:
2. Systemic anti-cancer therapy within 3 weeks or 5 half-lives prior to study entry,whichever is shorter.
3. Thoracic radiation therapy or significant surgery within 3 weeks prior to studyentry. Localized palliative radiotherapy for pain control in non-target lesionsis allowed during the screening period.
4. Received an investigational product or been treated with an investigationaldevice within 30 days prior to first drug administration or plans to participatein any other clinical trial while on this study.
5. Previous or concurrent malignancy that would prevent evaluation of the primaryendpoint (e.g. R/R hematological malignancy).
6. Patients whose extent of tumor or loculations would render intrapleural administrationincomplete and/or ineffective.
7. Known hypersensitivity to the active ingredient or any excipient contained in the drugformulation.
8. History or clinical evidence of any surgical or medical condition which theinvestigator and/or medical monitor judges as likely to interfere with the results ofthe study or pose an additional risk in participating, e.g., rapidly progressive oruncontrolled disease involving a major organ system-vascular, cardiac, pulmonary,gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine,or an immunodeficiency, or clinically significant active psychiatric or abusedisorders.
9. Active infection with human immunodeficiency virus (HIV) and CD4+ T-cell count < 350/μL. Patients not on established anti-retroviral therapy for at least four weeksprior to first dose of study drug and having a detectable HIV viral load. Testing isnot required for eligibility.
10. Active infection with hepatitis B (surface antigen); or infection with hepatitis C inabsence of sustained virologic response. Testing is not required for eligibility.
11. Pregnant or breast-feeding patients.
12. Patients with symptomatic or unstable CNS primary tumor or metastases and/orcarcinomatous meningitis. Patients with documented treated CNS metastases stable offsteroids may be enrolled at the discretion of the investigator.
13. Therapeutic oral anticoagulation for a thromboembolic event (prophylacticanticoagulation is allowed as long as patient can undergo catheter placement andbiopsy). LMWH is allowed on condition that it is medically acceptable to interruptLMWH therapy for all study procedures.
14. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15days or other immunosuppressive drugs within 3 weeks prior to start of the study.Inhaled and topical corticosteroids are permitted. Up to 10 mg/day prednisone orequivalent is permitted.