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dc.contributor.authorKristeleit, R
dc.contributor.authorEvans, J
dc.contributor.authorMolife, LR
dc.contributor.authorTunariu, N
dc.contributor.authorShaw, H
dc.contributor.authorSlater, S
dc.contributor.authorHaris, NRM
dc.contributor.authorBrown, NF
dc.contributor.authorForster, MD
dc.contributor.authorDiamantis, N
dc.contributor.authorRulach, R
dc.contributor.authorGreystoke, A
dc.contributor.authorAsghar, U
dc.contributor.authorRata, M
dc.contributor.authorAnderson, S
dc.contributor.authorBachmann, F
dc.contributor.authorHannah, A
dc.contributor.authorKaindl, T
dc.contributor.authorLane, HA
dc.contributor.authorLarger, PJ
dc.contributor.authorSchmitt-Hoffmann, A
dc.contributor.authorEngelhardt, M
dc.contributor.authorTzankov, A
dc.contributor.authorPlummer, R
dc.contributor.authorLopez, J
dc.coverage.spatialEngland
dc.date.accessioned2023-05-24T15:08:39Z
dc.date.available2023-05-24T15:08:39Z
dc.date.issued2020-08-03
dc.identifier10.1038/s41416-020-1010-8
dc.identifier.citationBritish Journal of Cancer, 2020, 123 (9), pp. 1360 - 1369en_US
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5804
dc.identifier.eissn1532-1827
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/s41416-020-1010-8
dc.description.abstractBACKGROUND: BAL101553 (lisavanbulin), the lysine prodrug of BAL27862 (avanbulin), exhibits broad anti-proliferative activity in human cancer models refractory to clinically relevant microtubule-targeting agents. METHODS: This two-part, open-label, phase 1/2a study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of 2-h infusion of BAL101553 in adults with advanced or recurrent solid tumours. The MTD was determined using a modified accelerated titration design in phase I. Patients received BAL101553 at the MTD and at lower doses in the phase 2a expansion to characterise safety and efficacy and to determine the recommended phase 2 dose (RP2D). RESULTS: Seventy-three patients received BAL101553 at doses of 15-80 mg/m2 (phase 1, n = 24; phase 2a, n = 49). The MTD was 60 mg/m2; DLTs observed at doses ≥60 mg/m2 were reversible Grade 2-3 gait disturbance with Grade 2 peripheral sensory neuropathy. In phase 2a, asymptomatic myocardial injury was observed at doses ≥45 mg/m2. The RP2D for 2-h intravenous infusion was 30 mg/m2. The overall disease control rate was 26.3% in the efficacy population. CONCLUSIONS: The RP2D for 2-h infusion of BAL101553 was well tolerated. Dose-limiting neurological and myocardial side effects were consistent with the agent's vascular-disrupting properties. CLINICAL TRIAL REGISTRATION: EudraCT: 2010-024237-23.
dc.formatPrint-Electronic
dc.format.extent1360 - 1369
dc.languageeng
dc.language.isoengen_US
dc.publisherSPRINGERNATUREen_US
dc.relation.ispartofBritish Journal of Cancer
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBenzimidazoles
dc.subjectDisease Progression
dc.subjectFemale
dc.subjectHumans
dc.subjectInfusions, Intravenous
dc.subjectM Phase Cell Cycle Checkpoints
dc.subjectMale
dc.subjectMaximum Tolerated Dose
dc.subjectMiddle Aged
dc.subjectNeoplasms
dc.subjectOxadiazoles
dc.subjectProdrugs
dc.subjectSpindle Apparatus
dc.subjectUnited Kingdom
dc.titlePhase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-07-16
dc.date.updated2023-05-24T14:35:51Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1038/s41416-020-1010-8en_US
rioxxterms.licenseref.startdate2020-08-03
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/32741975
pubs.issue9
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Early Phase Drug Development
pubs.publication-statusPublished
pubs.publisher-urlhttp://dx.doi.org/10.1038/s41416-020-1010-8
pubs.volume123
icr.researchteamEarly Phase Drug Developen_US
dc.contributor.icrauthorTunariu, Nina
dc.contributor.icrauthorLopez, Juanita
icr.provenanceDeposited by Ms Hilary Dent (impersonating Dr Juanita Lopez) on 2023-05-24. Deposit type is initial. No. of files: 1. Files: Phase 12a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours.pdf


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