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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Ixovex-1 is a novel oncolytic human adenovirus serotype 5.
Humanised antibody
The Royal Marsden
London, United Kingdom
RECRUITINGTo 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 \[Day 1 to 30 days after last dose\].
Time frame: 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 \[Day 1 to 30 days after last dose\].
Time frame: Through study completion, an average of 2 years
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).
Time frame: 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.
Time frame: Through study completion, an average of 2 years
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