Trial Title:
Ixovex-1 Single Agent and Combination Therapy
NCT ID:
NCT06549946
Condition:
Solid Tumor
Head and Neck Cancer
Conditions: Official terms:
Head and Neck Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Open-label, single agent therapy
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Ixovex-1
Description:
Ixovex-1 is a novel oncolytic human adenovirus serotype 5.
Arm group label:
Phase II
Arm group label:
Phase Ia
Arm group label:
Phase Ib
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Humanised antibody
Arm group label:
Phase II
Arm group label:
Phase Ib
Other name:
Keytruda
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. 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).
3. Subjects with injectable locally advanced, unresectable, or metastatic solid
tumours.
4. In Phase Ia and Phase Ib, all solid tumour types will be accepted.
5. For Phase II, all solid tumour types will be considered with an emphasis on
cutaneous squamous cell cancers and head and neck cancers.
6. 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.
7. A minimum of one tumour with a diameter of greater than 1 cm as measured by
ultrasound and/or clinical measurement.
8. All approved therapeutic options have been exhausted, are not available, are
unlikely to have significant clinical benefit or have been declined by the subject.
9. The Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
10. Life expectancy more than 6 months.
11. Pathologically documented, locally advanced, or metastatic solid malignancy.
12. Subject having laboratory values defined as:
1. White blood cell counts greater than 3,000/mm3 OR absolute neutrophil counts
greater than 1,500/mm3;
2. Platelet count greater than 100,000/mm3;
3. Haemoglobin greater than 9 g/dL (transfusions allowed if not used solely to
meet eligibility criteria);
4. Aspartate aminotransferase/alanine aminotransferase less than 2.5 times ULN;
5. Bilirubin no greater than 1.5 times ULN;
6. Creatinine clearance (Cockcroft-Gault formula) ≥50 mL/min.
13. Be willing and able to comply with scheduled visits, the treatment plan, imaging,
and laboratory tests.
Exclusion Criteria:
1. 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.
2. Tumours involving a major blood vessel where tumour necrosis might endanger the
subject.
3. Impaired cardiac function or clinically significant cardiac disease, including any
of the following:
1. 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.
2. Acute myocardial infarction or unstable angina pectoris <6 months prior to
study entry.
4. Subjects with interstitial pneumonia or history of drug-induced interstitial
pneumonia/pneumonitis.
5. Have an immune system disorder (known human immunodeficiency virus infection or
hepatitis B or C).
6. Chronic liver disease or chronic hepatitis (Child-Pugh class B or C hepatic
impairment).
7. 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.
8. Subjects receiving systemic chronic steroid therapy or any immunosuppressive therapy
(>10 mg/day prednisone or equivalent). Topical, inhaled, nasal, and ophthalmic
steroids are allowed.
9. Use of any live vaccines against infectious diseases within 4 weeks of initiation of
study treatment.
10. 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.
11. Active infection requiring systemic or antiviral or antibiotic therapy.
12. Subjects with active cytomegalovirus infection.
13. Prior therapy:
1. 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).
2. Did not recover from prior biologic therapy, endocrine therapy, or any prior
diagnostic or therapeutic procedures.
3. Received prior chemotherapy within 21 days of C1D1.
4. Previous treatment with oncolytic virotherapy.
14. Presence of CTCAE ≥ Grade 2 toxicity (except alopecia, peripheral neuropathy, and
ototoxicity, which are excluded if ≥ CTCAE Grade 3) due to prior cancer therapy.
15. Participation in an interventional, investigational study within 4 weeks or 5
half-lives (whichever is shorter) of the first dose of study treatment.
16. 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.
17. 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.
18. Known hypersensitivity to any component of Ixovex-1 or pembrolizumab (latter for
Phase 1b and Phase 2 only).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Royal Marsden
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Contact:
Last name:
Kevin Harrington
Email:
kevin.harrington@icr.ac.uk
Investigator:
Last name:
Kevin Harrington
Email:
Principal Investigator
Start date:
September 9, 2024
Completion date:
January 30, 2027
Lead sponsor:
Agency:
Psivac Ltd
Agency class:
Industry
Collaborator:
Agency:
IQVIA Biotech
Agency class:
Industry
Source:
Psivac Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06549946
