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

NCT05278975 | Unknown Phase 1 DMC

• 1 other identifier: RS-TS-101-01
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Malignant Pleural Effusion; Malignant Pleural Mesothelioma; Mesothelioma; Mesotheliomas Pleural; Mesothelioma; Lung; Pleural Effusion, Malignant

Outcome Measures

Primary Outcomes (3)

• Dose-limiting Toxicity

  The incidence of DLTs during the DLT assessment period.

  First 21 days of treatment.

• Frequency and Severity of Adverse Events (AE)

  The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.

  Screening to 90 days from last dose.

• Dose Finding

  Determination of the MTD and/or the RP2D.

  Screening to 90 days from last dose.

Secondary Outcomes (5)

• Pharmacokinetics of RSO-021

  Day 1 of dosing through 21 days post last dose.

• Pharmacokinetics of RSO-021

  Day 1 of dosing through 21 days post last dose.

• Objective Response Rate (ORR)

  Day 1 of dosing through day 90 after the last dose.

• Disease Control Rate (DCR)

  Day 1 of dosing through day 90 after the last dose.

• Progression Free Survival (PFS)

  Day 1 of dosing through day 90 after the last dose.

Study Arms (5)

Phase 1 - Dose Escalation

EXPERIMENTAL

RSO-021 administered in increasing doses as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle.

Drug: RSO-021

Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors

EXPERIMENTAL

RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from non-mesothelioma solid tumors.

Drug: RSO-021

Ph2 - Dose Expansion - MPE from mesothelioma

EXPERIMENTAL

RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from mesothelioma.

Drug: RSO-021

P2 - Dose Expansion - mesothelioma -First line treatment prior to Ipi/Nivo

EXPERIMENTAL

RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with mesothelioma. This local treatment with RSO-021 is prior to systemic treatment of Ipi/Nivo.

Drug: RSO-021

Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors combination with Paclitaxel

EXPERIMENTAL

RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from non-mesothelioma solid tumors. In combination with Paclitaxel. Paclitaxel will be administered as a systemic therapy per SoC and the approved labeling based on the tumor type being treated. Paclitaxel is commercially available in the UK

Drug: RSO-021

Interventions

RSO-021 DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

Also known as: Thiostrepton

P2 - Dose Expansion - mesothelioma -First line treatment prior to Ipi/Nivo; Ph2 - Dose Expansion - MPE from mesothelioma; Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors; Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors combination with Paclitaxel; Phase 1 - Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Last dose of prior anti-cancer therapies:
• Systemic anti-cancer therapy within 3 weeks or 5 half-lives prior to study entry, whichever is shorter.
• 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.
• 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.
• Previous or concurrent malignancy that would prevent evaluation of the primary endpoint (e.g. R/R hematological malignancy).
• Patients whose extent of tumor or loculations would render intrapleural administration incomplete and/or ineffective.
• Known hypersensitivity to the active ingredient or any excipient contained in the drug formulation.
• 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.
• 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.
• Active infection with hepatitis B (surface antigen); or infection with hepatitis C in absence of sustained virologic response. Testing is not required for eligibility.
• Pregnant or breast-feeding patients.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• RS Oncology LLC: lead

Study Sites (10)

South Mead North Bristol Hopsital

Bristol, BS105NB, United Kingdom

RECRUITING

NHS Greater Glasgow & Clyde

Glasgow, United Kingdom

RECRUITING

Leeds Teaching Hospital

Leeds, LS970F, United Kingdom

RECRUITING

Facility: HOPE Clinical Trials Facility, Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

Barts Health NHS Cancer Institute

London, EC1A7BE, United Kingdom

RECRUITING

Guys and St Thomas NHS Foundation Trust

London, SE19RT, United Kingdom

RECRUITING

The Royal Marsden

London, SW3 6JJ, United Kingdom

RECRUITING

The Christie NHS

Manchester, M204BX, United Kingdom

RECRUITING

Northumbria NorthTyne Side General Hospital

North Shields, NE29 8NH, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation

Oxford, OX42PG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pleural Effusion, Malignant; Mesothelioma, Malignant; Mesothelioma

Interventions

Thiostrepton

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Lung Neoplasms; Lung Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• James Spicer, MD

  Guys Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

George Naumov, PhD

CONTACT

(617) 835-5633; MITOPE@rsoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2022
• First Posted: March 15, 2022
• Study Start: March 31, 2022
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (10)