Trial of THEO-260 in Ovarian Cancer Patients

Official title

A Phase I/IIa, Open-label, Dose Finding, Safety, Tolerability and Exploratory Trial of THEO-260 in Patients With High Grade Serous or Endometrioid Ovarian Cancer

Overview

A research study evaluating a new oncolytic virus, THEO-260, in patients with advanced ovarian cancer. The trial will investigate different doses of THEO-260 administered intravenously to identify a dose that is safe, well tolerated, and exhibits preliminary evidence of anti tumour activity.

Interventions

• Biological THEO-260
  Oncolytic Virus

Primary outcome measures

• Safety and tolerability of THEO-260 [Part A] [Time frame: Until Day 28 after first dose]
• Establish recommended Phase 2 dose (RP2D) for THEO-260 [Part A] [Time frame: Estimated at 2 years]
• Evaluate preliminary efficacy of THEO-260 [Part B] [Time frame: Estimated at 16 weeks]

Secondary outcome measures (5)

• Pharmacokinetics (PK) of THEO-260 [Time frame: Estimated at 16 weeks]
• Shedding of THEO-260 [Time frame: Until Day 29 after first dose]
• Systemic CRS risk after THEO-260 [Time frame: Until Day 29 after first dose]
• Preliminary efficacy of THEO-260 [Part A] [Time frame: Estimated at 16 weeks]
• Safety and tolerability of THEO-260 [Part B] [Time frame: Until end of trial, estimated at 1 year after start of enrolment]

Eligibility criteria

Inclusion criteria

• Confirmed histological diagnosis of advanced high grade serous or endometrioid cancer of the fallopian tube, primary peritoneum or ovary either on archival biopsy or fresh tumour biopsy.
• Platinum-resistant disease (radiological recurrence/ progression with 6 months of prior platinum treatment), primary platinum-refractory disease (recurrence/ progression during first line platinum treatment) and patients who are intolerant to or have no available SOC or SOC unacceptable/ unsuitable in the view of the Investigator.
• Life expectancy of > 3 months.
• ECOG performance status of 0 or 1.
• Measurable disease as per RECIST V1.1.

Exclusion criteria

• Prior anti-cancer treatment within 28 days or 5 half-lives, prior to first dose of THEO-260.
• Prior treatment with a group B adenovirus.
• Currently enrolled in a clinical trial of an IMP or used any IMP with 5 half-live, prior to first dose of THEO-260.
• Radiation therapy within 2 weeks of first dose of THEO-260 and is scheduled to have radiation therapy during participation of trial.
• Clinical evidence of cerebral metastases or Central Nervous System (CNS) involvement including leptomeningeal disease. Patients with previous cerebral metastases must have no evidence of progression or haemorrhage after treatment.
• Uncontrolled pleural effusion or pericardial effusion requiring recurrent drainage procedures (as defined as once monthly or more frequently).
• Prior pneumonitis or history of interstitial lung disease.
• Confirmed QTcF ≥470 ms on screening 12-lead ECG or history of Torsades de Pointes or history of congenital long QT syndrome.
• Concomitant medications that prolong the QTc interval and/or increase the risk for Torsades de Pointes.
• Patients with active hepatitis infection or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection.
• Active infection with tuberculosis.
• Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).
• Patients with active human immunodeficiency virus (HIV) infection or known history of HIV infection.
• Active infection requiring IV antibiotics within 2 weeks prior to first dose of THEO-260, or long-term oral therapy for systemic infection.
• Known contra-indications or hypersensitivity to the excipients of the IMP.
• Viral infection during the 2 weeks prior to first dose of THEO-260.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• Known risk of renal injury, including those with a past history of acute or sub-acute renal disease.
• Known heart failure New York Heart Association (NYHA) Class 2-4.
• Known contra-indications or hypersensitivity to the AxMP, paracetamol.
• Known alcohol consumption in excess of 2 units per day.
• Left ventricular ejection fraction (LVEF) <50%, unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to trial enrolment or a history of myocarditis.
• Arterial oxygen saturation <92% on room air prior to first dose of THEO-260.
• Received any licensed or investigational vaccines within 28 days prior to first dose of THEO-260.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 3 centers

• The Beatson West of Scotland Cancer Centre — Glasgow
• Imperial College Healthcare NHS Trust, Hammersmith Hospital — London
• Oxford University Hospitals NHS Foundation Trust, Churchill Hospital — Oxford

Spain · 1 center

• Centro Integral Oncológico Clara Campal (CIOCC) Hospital — Madrid

Identifiers

NCT: NCT06618235 · THEO-260-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗