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. et al. (2022) 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, 127(1), pp. 92-101. (doi: 10.1038/s41416-022-01780-z) (PMID:35568736)

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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.

Item Type:Articles
Additional Information:Funding to the three centres of the UK ECMC network was provided by Cancer Research UK and the relevant UK devolved nation Department of Health. Invest Northern Ireland provided support through funding for the trial.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson, Professor Richard
Authors: El Helali, A., Plummer, R., Jayson, G. C., Coyle, V. M., Drew, Y., Mescallado, N., Harris, N., Clamp, A. R., McCann, J., Swaisland, H., Kennedy, R. D., Cranston, A. N., and Wilson, R. H.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Nature Research
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:14 May 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in British Journal of Cancer 127(1): 92-101
Publisher Policy:Reproduced under a Creative Commons License

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