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Ref Type Journal Article
PMID (33588149)
Authors Vidal L, Victoria I, Gaba L, Martín MG, Brunet M, Colom H, Cortal M, Gómez-Ferrería M, Yeste-Velasco M, Perez A, Rodon J, Sohal DPS, Lizcano JM, Domènech C, Alfón J, Gascón P
Title A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours.
Journal European journal of cancer (Oxford, England : 1990)
Vol 146
Issue
Date 2021 Feb 12
URL
Abstract Text ABTL0812 is an autophagy inducer that promotes cancer cell death by activation of cytotoxic autophagy selectively in tumour cells. ABTL0812 induces endoplasmic reticulum stress and blocks the Akt-mTOR axis; both actions converge to activate a robust and sustained autophagy leading to cancer cell death. Preclinical data supported the initiation of clinical trials in patients with cancer.This first-in-human trial consisted of an escalation phase (3 + 3 design), followed by an expansion phase, to assess safety and tolerability of ABTL0812. Secondary objectives were determining the recommended phase II dose (RP2D), clinical antitumour activity, pharmacokinetics (PK) and pharmacodynamics (PD).A total of 29 patients were enrolled and treated; fifteen patients were treated in four escalation dosing cohorts (ranging from 500 mg once a day to 2000 mg twice a day) and fourteen in the expansion phase (dosed with 1300 mg three times a day). No maximum tolerated dose was attained, and RP2D was determined by PK/PD modelling. Most drug-related adverse events were gastrointestinal grade I-II. Correlation between drug levels and pAkt/Akt ratio was found. Two cases of long-term (>1 year) stable disease were observed.ABTL0812 is safe and has an acceptable tolerability profile, allowing a long-term oral dosing. RP2D of 1300 mg three times a day was determined according to PK/PD modelling, and preliminary antitumour efficacy was observed.NCT02201823.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown Advanced Solid Tumor not applicable ABTL0812 Phase I Actionable In a Phase I/Ib trial, ABTL0812 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, resulted in long lasting stable disease for more than 1 year in two patients (PMID: 33588149; NCT02201823). 33588149
Unknown unknown cholangiocarcinoma not applicable ABTL0812 Case Reports/Case Series Actionable In a Phase I/Ib trial, ABTL0812 treatment resulted in stable disease lasted for 78 weeks in a patient with cholangiocarcinoma (PMID: 33588149; NCT02201823). 33588149
Unknown unknown endometrial carcinoma not applicable ABTL0812 Case Reports/Case Series Actionable In a Phase I/Ib trial, ABTL0812 treatment resulted in stable disease lasted for 59 weeks in a patient with endometrioid endometrial cancer (PMID: 33588149; NCT02201823). 33588149