Ixovex-1 Single Agent and Combination Therapy

NCT06549946 | Recruiting Phase 1 DMC

• 1 other identifier: Ixovex-1-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, dose de-escalating, non-randomised, multi-centre phase I/II study to determine safety and efficacy of the oncolytic virus, Ixovex-1 administered by intratumoural (IT) injection. This will be assessed in patients with palpable locally advanced, unresectable, or metastatic tumours, for whom all approved therapeutic options have been exhausted, are not available, are unlikely to have significant clinical benefit, or are declined by the patient.

Conditions

Solid Tumor; Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• To determine the safety profile of Ixovex-1 when administered by intratumoural injection alone or in combination with Pembrolizumab in patients with unresectable, locally advanced, or metastatic solid tumours.

  Percentage of subjects with DLTs during the DLT period \[Day 1 to Day 28\]. Percentage of subjects with SAEs, overall and by maximum severity \[Day 1 to 30 days after last dose\]. Percentage of subjects with TEAEs, overall and by maximum severity \[Day 1 to 30 days after last dose\].

  Through study completion, an average of 2 years

• To determine the MTD and recommended Phase 2 dose of Ixovex-1.

  Percentage of subjects with TEAEs, overall and by maximum severity \[Day 1 to 30 days after last dose\].

  Through study completion, an average of 2 years

Secondary Outcomes (2)

• To assess clinical efficacy using a combination of radiological imaging, medical photography, and histology.

  Through study completion, an average of 2 years

• Assessment of antitumour effects in injected tumours and in non-injected tumours.

  Through study completion, an average of 2 years

Study Arms (3)

Phase Ia

EXPERIMENTAL

In Phase Ia, subjects will receive Ixovex-1 intratumourally.

Biological: Ixovex-1

Phase Ib

EXPERIMENTAL

In Phase Ib, subjects will receive combination therapy with Ixovex-1 intratumourally and Pembrolizumab at the standard dose.

Biological: Ixovex-1; Biological: Pembrolizumab

Phase II

EXPERIMENTAL

In Phase II, subjects will receive combination therapy with Ixovex-1 intratumourally and Pembrolizumab at the standard dose.

Biological: Ixovex-1; Biological: Pembrolizumab

Interventions

Ixovex-1 BIOLOGICAL

Ixovex-1 is a novel oncolytic human adenovirus serotype 5.

Phase II; Phase Ia; Phase Ib

Pembrolizumab BIOLOGICAL

Humanised antibody

Also known as: Keytruda

Phase II; Phase Ib

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Have signed an informed consent indicating that the subject is aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• Female or male subjects aged ≥18 years (local regulatory requirements should be followed if the legal age of consent for study participation is \>18 years old).
• Subjects with injectable locally advanced, unresectable, or metastatic solid tumours.
• In Phase Ia and Phase Ib, all solid tumour types will be accepted.
• For Phase II, all solid tumour types will be considered with an emphasis on cutaneous squamous cell cancers and head and neck cancers.
• Subjects with at least 1 measurable tumour (per RECIST 1.1) cutaneous/subcutaneous/nodal tumour suitable for direct percutaneous injection. Subjects may have other sites of disease.
• A minimum of one tumour with a diameter of greater than 1 cm as measured by ultrasound and/or clinical measurement.
• All approved therapeutic options have been exhausted, are not available, are unlikely to have significant clinical benefit or have been declined by the subject.
• The Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Life expectancy more than 6 months.
• Pathologically documented, locally advanced, or metastatic solid malignancy.
• Subject having laboratory values defined as:
• White blood cell counts greater than 3,000/mm3 OR absolute neutrophil counts greater than 1,500/mm3;
• Platelet count greater than 100,000/mm3;
• Haemoglobin greater than 9 g/dL (transfusions allowed if not used solely to meet eligibility criteria);

You may not qualify if:

• Presence of overt leptomeningeal or active central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (eg, radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Subjects with treated brain metastases should be neurologically stable (for 4 weeks post treatment and prior to study enrolment) and off steroids for at least 2 weeks before administration of any study treatment.
• Tumours involving a major blood vessel where tumour necrosis might endanger the subject.
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (New York Heart Association Grade ≥2), left ventricular ejection fraction \<50% as determined by multiple gated acquisition (MUGA) or echocardiogram (ECHO), uncontrolled hypertension, or clinically significant arrhythmia.
• Acute myocardial infarction or unstable angina pectoris \<6 months prior to study entry.
• Subjects with interstitial pneumonia or history of drug-induced interstitial pneumonia/pneumonitis.
• Have an immune system disorder (known human immunodeficiency virus infection or hepatitis B or C).
• Chronic liver disease or chronic hepatitis (Child-Pugh class B or C hepatic impairment).
• Subjects receiving systemic chronic steroid therapy or any immunosuppressive therapy (\>10 mg/day prednisone or equivalent). Topical, inhaled, nasal, and ophthalmic steroids are allowed.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
• Subjects with a history of stroke or having active neurological symptoms, with the exception of chronic conditions which, in the opinion of the neurologist, Investigator, and the Sponsor, would not impact ongoing neurologic assessments while on study treatment.
• Active infection requiring systemic or antiviral or antibiotic therapy.
• Subjects with active cytomegalovirus infection.
• Prior therapy:
• Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).

Sponsors & Collaborators

• Psivac Ltd: lead
• IQVIA Biotech: collaborator

Study Sites (1)

The Royal Marsden

London, SW3 6JJ, United Kingdom

RECRUITING

Related Publications (1)

• Anwar M, Arendt ML, Ramachandran M, Carlsson A, Essand M, Akusjarvi G, Alusi G, Oberg D. Ixovex-1, a novel oncolytic E1B-mutated adenovirus. Cancer Gene Ther. 2022 Nov;29(11):1628-1635. doi: 10.1038/s41417-022-00480-3. Epub 2022 May 20.

  PMID: 35596069 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Kevin Harrington

  The Royal Marsden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Imad Mardini

CONTACT

+44 20 7971 1100; i.mardini@psivac.com

Study Design

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

Model Details: Open-label, single agent therapy

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 12, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)