Overview

This is an open-label, non-randomized, multicenter, translational Phase 1/2 dose-escalation and expansion study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RSO-021 after intrapleural (IP) administration in patients with malignant pleural effusion (MPE) (non-mesothelioma) and MPE from mesothelioma.

Eligibility

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:

   1. only patients with breast cancer, ovarian cancer or non-small cell lung cancer.
   2. patients for whom paclitaxel is a recommended SoC therapy.
   3. no contraindications to paclitaxel.
4. 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.
          1. Patients enrolled in the mesothelioma expansion phase will be requested to undergo a
             tumor biopsy during the screening period and after the third dose.
          2. 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.
        Exclusion Criteria:
          1. Last dose of prior anti-cancer therapies:
               1. Systemic anti-cancer therapy within 3 weeks or 5 half-lives prior to study entry,
                  whichever is shorter.
               2. Thoracic radiation therapy or significant surgery within 3 weeks prior to study
                  entry. Localized palliative radiotherapy for pain control in non-target lesions
                  is allowed during the screening period.
               3. Received an investigational product or been treated with an investigational
                  device within 30 days prior to first drug administration or plans to participate
                  in any other clinical trial while on this study.
          2. Previous or concurrent malignancy that would prevent evaluation of the primary
             endpoint (e.g. R/R hematological malignancy).
          3. Patients whose extent of tumor or loculations would render intrapleural administration
             incomplete and/or ineffective.
          4. Known hypersensitivity to the active ingredient or any excipient contained in the drug
             formulation.
          5. History or clinical evidence of any surgical or medical condition which the
             investigator and/or medical monitor judges as likely to interfere with the results of
             the study or pose an additional risk in participating, e.g., rapidly progressive or
             uncontrolled 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 abuse
             disorders.
          6. 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 weeks
             prior to first dose of study drug and having a detectable HIV viral load. Testing is
             not required for eligibility.
          7. Active infection with hepatitis B (surface antigen); or infection with hepatitis C in
             absence of sustained virologic response. Testing is not required for eligibility.
          8. Pregnant or breast-feeding patients.
          9. Patients with symptomatic or unstable CNS primary tumor or metastases and/or
             carcinomatous meningitis. Patients with documented treated CNS metastases stable off
             steroids may be enrolled at the discretion of the investigator.
         10. Therapeutic oral anticoagulation for a thromboembolic event (prophylactic
             anticoagulation is allowed as long as patient can undergo catheter placement and
             biopsy). LMWH is allowed on condition that it is medically acceptable to interrupt
             LMWH therapy for all study procedures.
         11. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15
             days 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 or
             equivalent is permitted.