Solid TumorPhase 1/2IXACTNCT06549946
Ixovex-1 Single Agent and Combination Therapy
A Phase 1/2 study testing Ixovex-1 and Pembrolizumab in people with Solid Tumor and Head and Neck Cancer, run by Psivac Ltd at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Head and Neck Cancer
- What is being tested?
- Ixovex-1 and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Dec 2024to 30 Jan 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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);
- Aspartate aminotransferase/alanine aminotransferase less than 2.5 times ULN;
- Bilirubin no greater than 1.5 times ULN;
- Creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min.
- Be willing and able to comply with scheduled visits, the treatment plan, imaging, and laboratory tests.
Who cannot join
- 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.
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- 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).
- Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
- 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).
- Did not recover from prior biologic therapy, endocrine therapy, or any prior diagnostic or therapeutic procedures.
- Received prior chemotherapy within 21 days of C1D1.
- Previous treatment with oncolytic virotherapy.
- Presence of CTCAE ≥ Grade 2 toxicity (except alopecia, peripheral neuropathy, and ototoxicity, which are excluded if ≥ CTCAE Grade 3) due to prior cancer therapy.
- Participation in an interventional, investigational study within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment.
- Any medical condition that would, in the Investigator's judgement, prevent the subject's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results.
- Pregnant or breastfeeding woman (pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test). Female subjects of childbearing potential must agree to use highly effective contraception (during the study and for 6 months from last dose of Ixovex-1), must be surgically sterile, or must be postmenopausal. Male subjects must use a condom (during the study and for 6 months from last dose of Ixovex-1) or be surgically sterile. Additionally, female partners may be requested to use highly effective contraception as an additional safeguard. For Pembrolizumab, the manufacturer recommends contraception for women of childbearing age during treatment with Pembrolizumab and for 4 months post last treatment of Pembrolizumab. For Pembrolizumab, the manufacturer recommends contraception for male subjects during treatment with Pembrolizumab and for 4 months post last treatment of Pembrolizumab.
- Known hypersensitivity to any component of Ixovex-1 or pembrolizumab (latter for Phase 1b and Phase 2 only).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
The Royal Marsden
London, SW3 6JJ
Kevin Harrington, kevin.harrington@icr.ac.uk
Kevin Harrington
About this study
Official title: A Phase I/II Open-label, Clinical Trial of Intratumoural Ixovex-1 as Single Agent Therapy or in Combination With Pembrolizumab in Palpable Solid Tumours
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.
Read the detailed description
The Phase Ia arm of the study will employ a modified 3+3 dose de-escalation design. At least six subjects will receive intratumoural injections of Ixovex-1 approximately every 2 weeks over a period of 8 weeks (4 treatments) to determine the maximum tolerated dose (MTD).
The Phase Ib arm of the study will also employ a modified 3+3 dose de-escalation design. At least six subjects will be treated with Ixovex-1 (MTD from Phase Ia) in combination with standard dosing of Pembrolizumab to determine the recommended phase 2 dose (RP2D) for the combination therapy. Subjects will receive a total of 4 doses of Ixovex-1 and 8 doses of Pembrolizumab. Two treatments of Ixovex-1 will be given prior to commencing Pembrolizumab, and 2 treatments will be given in combination with the first 2 Pembrolizumab standard infusions administered every 3 weeks. The subsequent 6 doses of Pembrolizumab will be administered without Ixovex-1 every 3 weeks thereafter.
The Phase II arm of the study will use a Simon Type II study design to assess the RP2D of Ixovex-1 in combination with Pembrolizumab, as determined in Phase Ib. This will initially involve 6 subjects, with the potential to expand to 18 subjects in specific tumor types where clinical benefit or a positive treatment response is observed, such as in subjects who have previously been refractory to immunotherapy.
- Conditions
- Solid Tumor, Head and Neck Cancer
- Being tested
- Ixovex-1, Pembrolizumab
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ixovex-1Biological
Ixovex-1 is a novel oncolytic human adenovirus serotype 5.
PembrolizumabBiological
Also called Keytruda
Humanised antibody
| Study group | Role | What they receive |
|---|---|---|
| Phase Ia | Experimental | In Phase Ia, subjects will receive Ixovex-1 intratumourally. Receives: Biological: Ixovex-1 |
| Phase Ib | Experimental | In Phase Ib, subjects will receive combination therapy with Ixovex-1 intratumourally and Pembrolizumab at the standard dose. Receives: 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. Receives: Biological: Ixovex-1; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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].
Measured: 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].
Measured: 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.
Overall response rate (CR + PR).
Best overall confirmed response - percentage of subjects at each response level (CR, PR, SD, PD).
Measured: Through study completion, an average of 2 years
Assessment of antitumour effects in injected tumours and in non-injected tumours.
Change in cumulative tumour size.
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2024
- Study start17 Dec 2024
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Open-label, single agent therapy
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Psivac Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Biotech
- Responsible party
- Sponsor
- Investigators
- Kevin Harrington, Principal investigator, The Royal Marsden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06549946
- Sponsor's protocol ID
- Ixovex-1-01
- Acronym
- IXACT
- Status last verified
- Jan 2025
- First submitted
- 30 Jul 2024
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35596069
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open-label, Clinical Trial of Intratumoural Ixovex-1 as Single Agent Therapy or in Combination With Pembrolizumab in Palpable Solid Tumours
- ClinicalTrials.gov ID
- NCT06549946
- Acronym / sponsor ID
- IXACT / Ixovex-1-01
- Conditions
- Solid Tumor, Head and Neck Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Psivac LtdIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Biotech
- Study start
- 17 Dec 2024 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 12 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The Phase Ia arm of the study will employ a modified 3+3 dose de-escalation design. At least six subjects will receive intratumoural injections of Ixovex-1 approximately every 2 weeks over a period of 8 weeks (4 treatments) to determine the maximum tolerated dose (MTD).
The Phase Ib arm of the study will also employ a modified 3+3 dose de-escalation design. At least six subjects will be treated with Ixovex-1 (MTD from Phase Ia) in combination with standard dosing of Pembrolizumab to determine the recommended phase 2 dose (RP2D) for the combination therapy. Subjects will receive a total of 4 doses of Ixovex-1 and 8 doses of Pembrolizumab. Two treatments of Ixovex-1 will be given prior to commencing Pembrolizumab, and 2 treatments will be given in combination with the first 2 Pembrolizumab standard infusions administered every 3 weeks. The subsequent 6 doses of Pembrolizumab will be administered without Ixovex-1 every 3 weeks thereafter.
The Phase II arm of the study will use a Simon Type II study design to assess the RP2D of Ixovex-1 in combination with Pembrolizumab, as determined in Phase Ib. This will initially involve 6 subjects, with the potential to expand to 18 subjects in specific tumor types where clinical benefit or a positive treatment response is observed, such as in subjects who have previously been refractory to immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open-label, single agent therapy
| Arm | Type | Receives |
|---|---|---|
| Phase Ia | Experimental | Biological: Ixovex-1In Phase Ia, subjects will receive Ixovex-1 intratumourally. |
| Phase Ib | Experimental | Biological: Ixovex-1, Biological: PembrolizumabIn Phase Ib, subjects will receive combination therapy with Ixovex-1 intratumourally and Pembrolizumab at the standard dose. |
| Phase II | Experimental | Biological: Ixovex-1, Biological: PembrolizumabIn Phase II, subjects will receive combination therapy with Ixovex-1 intratumourally and Pembrolizumab at the standard dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (24 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ixovex-1Ixovex-1 is a novel oncolytic human adenovirus serotype 5. | Biological | Phase II, Phase Ia, Phase Ib |
| PembrolizumabAlso: KeytrudaHumanised antibody | Biological | Phase II, Phase Ib |
Primary outcome
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.
Time frame: Through study completion, an average of 2 years
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].
To determine the MTD and recommended Phase 2 dose of Ixovex-1.
Time frame: Through study completion, an average of 2 years
Percentage of subjects with TEAEs, overall and by maximum severity [Day 1 to 30 days after last dose].
2 secondary outcomes
To assess clinical efficacy using a combination of radiological imaging, medical photography, and histology.
Time frame: Through study completion, an average of 2 years
Assessment of antitumour effects in injected tumours and in non-injected tumours.
Time frame: Through study completion, an average of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Background: PubMed 35596069Anwar 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kevin Harrington principal investigator
The Royal Marsden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ixovex-1 and Pembrolizumab in people with Solid Tumor and Head and Neck Cancer, run by Psivac Ltd at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Imad Mardini (+44 20 7971 1100, i.mardini@psivac.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Through study completion, an average of 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06549946, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.