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- Ekman, Simon, et al.
(author)
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Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor : Experiences in patients with squamous non-small cell lung carcinoma
- 2011
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 50:3, s. 441-447
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Journal article (peer-reviewed)abstract
- Background. Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. PPP is currently tested as an orally administrated single agent treatment in an open-label combined Phase I/II clinical study in advanced cancer patients with solid tumors which progress in spite of several lines of treatment. Patients and methods. The first part (Phase IA) consisted of single day BID dosing every three weeks with consecutive dose escalations. The second part (Phase IB) consists of seven days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing patients could continue treatment within a compassionate use setting. Results and discussion. The present report describes our experience with the four patients with progressive squamous non-small cell lung cancer (NSCLC) that have received treatment with PPP. Despite more than seven months of PPP treatment as third or fourth line treatment, the reported patients did not develop any additional metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography (PET) scans of the patients demonstrated large central necrotic areas, which may suggest tumor response. At the same time, the study drug is so far well tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response has not been reported before in anti-IGF-1R treatment and will be subject to further studies in the present clinical trial.
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| 2. |
- Öhnstedt, Emelie, et al.
(author)
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Engineered bacteria to accelerate wound healing : an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial
- 2023
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In: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 60
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Journal article (peer-reviewed)abstract
- Background: Impaired wound healing is a growing medical problem and very few approved drugs with documented clinical efficacy are available. CXCL12-expressing lactic acid bacteria, Limosilaoocillus reuteri (ILP100-Topical), has been demonstrated to accelerate wound healing in controlled preclinical models. In this first-in-human study, the primary objective was to determine safety and tolerability of the drug candidate ILP100-Topical, while secondary objectives included assessments of clinical and biologic effects on wound healing by traditionally accepted methods and explorative and traceable assessments.Methods: SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial (EudraCT 2019-000680-24) consisting of a single (SAD) and a multiple ascending dose (MAD) part of three dose cohorts each. The study was performed at the Phase 1 Unit, Uppsala University Hospital, Uppsala, Sweden. Data in this article were collected between Sep 20th, 2019 and Oct 20th 2021. In total 240 wounds were induced on the upper arms in 36 healthy volunteers. SAD: 12 participants, 4 wounds (2/arm), MAD: 24 participants, 8 wounds (4/arm). Wounds in each participant were randomised to treatment with placebo/saline or ILP100-Topical.Findings: In all individuals and doses, ILP100-Topical was safe and well-tolerated with no systemic exposure. A combined cohort analysis showed a significantly larger proportion of healed wounds (p = 0.020) on Day 32 by multi-dosing of ILP100-Topical when compared to saline/placebo (76% (73/96) and 59% (57/96) healed wounds, respectively). In addition, time to first registered healing was shortened by 6 days on average, and by 10 days at highest dose. ILP100-Topical increased the density of CXCL12+ cells in the wounds and local wound blood perfusion.Interpretation: The favourable safety profile and observed effects on wound healing support continued clinical development of ILP100-Topical for the treatment of complicated wounds in patients.
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