ArticleBritish journal of cancer2018
Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01110486 (A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy, in Combination With Carboplatin or in Combination With Docetaxel in Subjects With Advanced Solid Tumors), which is not on this map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy, in Combination With Carboplatin or in Combination With Docetaxel in Subjects With Advanced Solid Tumors
Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
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- The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.Molecules (Basel, Switzerland) · 2023Review
- Aurora B Inhibitors as Cancer Therapeutics.Molecules (Basel, Switzerland) · 2023Review
- Role of protein phosphorylation in cell signaling, disease, and the intervention therapy.MedComm · 2022Review
- Aurora B kinase: a potential drug target for cancer therapy.Journal of cancer research and clinical oncology · 2021Review
- Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.Cancers · 2021Article
- Second-Generation Antimitotics in Cancer Clinical Trials.Pharmaceutics · 2021Review
- Dual Kinase Targeting in Leukemia.Cancers · 2021Review
- First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundIlorasertib (ABT-348) inhibits Aurora and VEGF receptor (VEGFR) kinases. Patients with advanced solid tumours participated in a phase 1 dose-escalation trial to profile the safety, tolerability, and pharmacokinetics of ilorasertib.
methodsIlorasertib monotherapy was administered at 10-180 mg orally once daily (Arm I, n = 23), 40-340 mg orally twice daily (Arm II, n = 28), or 8-32 mg intravenously once daily (Arm III, n = 7), on days 1, 8, and 15 of each 28-day cycle.
resultsDose-limiting toxicities were predominantly related to VEGFR inhibition. The most frequent treatment-emergent adverse events ( > 30%) were: fatigue (48%), anorexia (34%), and hypertension (34%). Pharmacodynamic markers suggested that ilorasertib engaged VEGFR2 and Aurora B kinase, with the VEGFR2 effects reached at lower doses and exposures than Aurora inhibition effects. In Arm II, one basal cell carcinoma patient (40 mg twice daily (BID)) and one patient with adenocarcinoma of unknown primary site (230 mg BID) had partial responses.
conclusionsIn patients with advanced solid tumours, ilorasertib treatment resulted in evidence of engagement of the intended targets and antitumour activity, but with maximum inhibition of VEGFR family kinases occurring at lower exposures than typically required for inhibition of Aurora B in tissue. CLINICAL
trial registrationNCT01110486.
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