• Male or female ≥ 18 years old.

• ECOG performance status 0-1.

• Histological diagnosis of solid tumor/mesothelioma with MPE.

• Expansion Cohort 2:

⁃ only patients with breast cancer, ovarian cancer or non-small cell lung cancer.

⁃ patients for whom paclitaxel is a recommended SoC therapy.

⁃ no contraindications to paclitaxel.

• Patients with a disease burden that is predominantly pleural, and a pleural space that is accessible.

‣ Expansion Cohorts 1 and 2: MPE (non-mesothelioma): patients must have received at least 1 prior standard of care treatment regimen for advanced, unresectable malignancy, with documented progression.

‣ Expansion Cohort 3:

‣ MPE mesothelioma: patients must have received at least 1 prior standard-of-care treatment regimen for advanced, unresectable malignancy, with documented progression and there is no approved life extending alternative available.

‣ Expansion Cohort 4: MPE mesothelioma 'window of opportunity': patients should be treatment naïve, have refused or not be immediately requiring of systemic therapy and should be patients for whom drainage is planned immediately while further treatment options are arranged. It must be documented for each patient that protocol participation will not affect their subsequent ability to access standard systemic first line therapy due to RSO-021 being a local therapy.

‣ 6\. Resolution of all acute reversible toxic effects of prior therapy or surgical procedure to Grade ≤1 (except alopecia).

‣ 7\. For dose escalation: Archival paraffin block, ideally from the patient's most recent biopsy, should be provided prior to the first dose of study therapy, if sufficient tissue is available.

‣ For dose expansion cohorts: fresh tumor biopsy must be obtained.

• Patients enrolled in the mesothelioma expansion phase will be requested to undergo a tumor biopsy during the screening period and after the third dose.

• Patients enrolled in the non-mesothelioma expansion phase will be requested to undergo a tumor biopsy during the screening period and after the third dose only if medically feasible.

• 8\. Patients must have adequate organ function.