دورية أكاديمية
أعرض في EDS

Eftozanermin alfa (ABBV-621) monotherapy in patients with previously treated solid tumors: findings of a phase 1, first-in-human study.

التفاصيل البيبلوغرافية
العنوان: Eftozanermin alfa (ABBV-621) monotherapy in patients with previously treated solid tumors: findings of a phase 1, first-in-human study.
المؤلفون: LoRusso P; Yale Cancer Center, New Haven, CT, USA., Ratain MJ; University of Chicago, Chicago, IL, USA., Doi T; National Cancer Center Hospital East, Kashiwa, Japan., Rasco DW; START, San Antonio, TX, USA., de Jonge MJA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Moreno V; START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain., Carneiro BA; Lifespan Cancer Institute, Cancer Center at Brown University, Providence, RI, USA., Devriese LA; Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Petrich A; AbbVie Inc, North Chicago, IL, USA., Modi D; AbbVie Inc, North Chicago, IL, USA., Morgan-Lappe S; AbbVie Inc, North Chicago, IL, USA., Nuthalapati S; AbbVie Inc, North Chicago, IL, USA., Motwani M; AbbVie Inc, North Chicago, IL, USA., Dunbar M; AbbVie Inc, North Chicago, IL, USA., Glasgow J; AbbVie Inc, North Chicago, IL, USA., Medeiros BC; AbbVie Inc, North Chicago, IL, USA., Calvo E; START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. emiliano.calvo@startmadrid.com.
المصدر: Investigational new drugs [Invest New Drugs] 2022 Aug; Vol. 40 (4), pp. 762-772. Date of Electronic Publication: 2022 Apr 25.
نوع المنشور: Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 8309330 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-0646 (Electronic) Linking ISSN: 01676997 NLM ISO Abbreviation: Invest New Drugs Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Springer
Original Publication: Boston : M. Nijhoff, 1983-
مواضيع طبية MeSH: Antineoplastic Agents*/adverse effects , Neoplasms*/metabolism, Dose-Response Relationship, Drug ; Fatigue/chemically induced ; Humans ; Maximum Tolerated Dose ; Nausea/chemically induced
مستخلص: Eftozanermin alfa (eftoza), a second-generation tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) agonist, induces apoptosis in tumor cells by activation of death receptors 4/5. This phase 1 dose-escalation/dose-optimization study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of eftoza in patients with advanced solid tumors. Patients received eftoza 2.5-15 mg/kg intravenously on day 1 or day 1/day 8 every 21 days in the dose-escalation phase, and 1.25-7.5 mg/kg once-weekly (QW) in the dose-optimization phase. Dose-limiting toxicities (DLTs) were evaluated during the first treatment cycle to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Pharmacodynamic effects were evaluated in circulation and tumor tissue. A total of 105 patients were enrolled in the study (dose-escalation cohort, n = 57; dose-optimization cohort, n = 48 patients [n = 24, colorectal cancer (CRC); n = 24, pancreatic cancer (PaCA)]). In the dose-escalation cohort, seven patients experienced DLTs. MTD and RP2D were not determined. Most common treatment-related adverse events were increased alanine aminotransferase and aspartate aminotransferase levels, nausea, and fatigue. The one treatment-related death occurred due to respiratory failure. In the dose-optimization cohort, three patients (CRC, n = 2; PaCA, n = 1) had a partial response. Target engagement with regard to receptor saturation, and downstream apoptotic pathway activation in circulation and tumor were observed. Eftoza had acceptable safety, evidence of pharmacodynamic effects, and preliminary anticancer activity. The 7.5-mg/kg QW regimen was selected for future studies on the basis of safety findings, pharmacodynamic effects, and biomarker modulations. (Trial registration number: NCT03082209 (registered: March 17, 2017)).
(© 2022. The Author(s).)
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معلومات مُعتمدة: UL1 TR001863 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Apoptosis; Dose-escalation; Dose-optimization; Phase 1; Solid tumor; TRAIL-R agonist
سلسلة جزيئية: ClinicalTrials.gov NCT03082209
المشرفين على المادة: 0 (Antineoplastic Agents)
تواريخ الأحداث: Date Created: 20220425 Date Completed: 20220719 Latest Revision: 20230325
رمز التحديث: 20230327
مُعرف محوري في PubMed: PMC9035501
DOI: 10.1007/s10637-022-01247-1
PMID: 35467243
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-0646
DOI:10.1007/s10637-022-01247-1