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A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide, ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours
El Helali, A. Plummer, R. Jayson, Gordon C Coyle, V. M. Drew, Y. Mescallado, Nerissa Harris, N. Clamp, Andrew R McCann, J. Swaisland, H.
El Helali, A.
Plummer, R.
Jayson, Gordon C
Coyle, V. M.
Drew, Y.
Mescallado, Nerissa
Harris, N.
Clamp, Andrew R
McCann, J.
Swaisland, H.
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Abstract
Background: We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide.
Methods: We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours.
Results: Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10-300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1-2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3-18) weeks. Four of 18 evaluable patients (22%) had stable disease.
Conclusions: Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.
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Date
2022
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El Helali A, Plummer R, Jayson GC, Coyle VM, Drew Y, Mescallado N, et al. A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide, ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours. British Journal of Cancer. Springer Science and Business Media LLC; 2022.