Publications

Phase 1 of ABTL0812, a proautophagic drug, in combination with paclitaxel and carboplatin at first-line in advanced endometrial cancer and squamous cell lung carcinoma

Author(s): Lorena Farinas-Madrid, Purificación Estévez-García, Jose Alejandro Perez-Fidalgo, Joaquim Bosch-Barrera, Teresa Moran, Ernest Nadal, Victor Rodriguez Freixinos, Elisa Calvo, Alejandro Falcon, Paloma Martín-Martorell, Marisol Huerta Alvaro, Maria Pilar Barretina-Ginesta, Margarita Romeo, Marta Gil-Martin, Elena Garralda, Jordi Rodon, Jose M. Lizcano, Carles Domenech, Jose Alberto Alfon, Ana Oaknin; Vall d’Hebron University Hospital Institute of Oncology (VHIO), Barcelona, Spain; Unidad de Tumores Ginecológicos y Genitourinarios, Servicio de Oncologia Médica, Hospital Universitario Virgen del Rocío, Seville, Spain; INCLIVA Research Institute and Hospital Clínico Universitario de Valencia, Valencia, Spain; Institut Catala d'Oncologia, Universitary Hospital Dr. Josep Trueta, Girona, Spain; Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain; Institut Català d’Oncologia, L’Hospitalet, Barcelona, Spain; Vall d'Hebron Institut of Oncology, Barcelona, Spain; Servicio de Oncologia Médica, Hospital Universitario Virgen del Rocío, Seville, Spain; Medical Oncology Department. Hospital Universitario Virgen del Rocío, Seville, Spain; Hospital Clinic Universitario de Valencia, Valencia, Spain; Oncología Médica, Hospital Universitario de Valencia, Valencia, Spain; Medical Oncology Department, Catalan Institute of Oncology, Girona, Spain; Medical Oncology Department, Institut Català d’Oncologia (ICO) Badalona, B-ARGO, Badalona, Spain; Institut Català d'Oncologia-ICO L’Hospitalet, Barcelona, Spain; Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Institut de Neurociencies, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Ability Pharmaceuticals, Barcelona, Spain; Ability Pharmaceuticals SL, Cerdanyola Del Valles, Spain; Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

Meeting: 2019 ASCO Annual Meeting - Abstract No: 3089 - Poster Board Number: Poster Session (Board 81) - Citation: J Clin Oncol 37, 2019 (suppl; abstr 3089)

Abstract:
 

Background: ABTL0812 is a novel anti-cancer agent that induces a strong autophagy-mediated cell death by a dual mechanism. It inhibits the Akt/mTOR axis by upregulating TRIB3, an endogenous Akt inhibitor, and induces reticular (ER)-stress. Preclinical data in squamous non-small cell lung carcinoma (Sq-NSCLC) and endometrial cancer (EC) has indicated drug efficacy as a single agent and potentiation of chemotherapy. Methods: A phase 1 clinical study was designed where ABTL0812 was administered orally in combination with 175 mg/m2paclitaxel/carboplatin AUC5 D1 every 3 weeks (P/C), and posterior ABTL0812 as a maintenance therapy until disease progression or unacceptable toxicity. The study included first-line patients (pts) with advanced Sq-NSCLC or advanced/recurrent EC. The design included a 3+3 de-escalation trial followed by an expansion cohort, where the starting dose of ABTL0812 was 1300 mg tid and if at least 2 pts experienced a DLT, the dose level would be de-escalated to 1000 mg tid. Safety and tolerability were the primary endpoints and preliminary efficacy according to RECIST v1.1 criteria and pharmacodynamic biomarkers (TRIB3 and CHOP an ER-stress biomarker, by qPCR in whole blood) were the secondary endpoints. Results: 16 EC and 5 Sq-NSCLC pts were enrolled. One DLT, a grade 4 neutropenia, appeared in the first cohort of 6 pts and no de-escalation was applied. Fourteen pts were included in an expansion cohort with the same dose level (1300 mg tid), and 1 DLT, a grade 3 febrile neutropenia, was observed. Therefore, the dose of 1300 mg tid was selected as RP2D in combination with P/C. Most frequent grades 2-4 AEs were neutrophil count decreased (n = 9, 43%), nausea (n = 5, 24%), fatigue (n = 4, 19%), followed by anemia, vomiting, dyspepsia, platelet count decreased, arthralgia and neurotoxicity (n = 2, 10% each). Seventeen pts (13 EC and 4 Sq-NSCLC) who completed at least two treatment cycles were evaluable for efficacy; 1 CR (EC), 8 PR (7 EC and 1 Sq-NSCLC), 7 SD (5 EC and 2 Sq-NSCLC) and 1 PD (Sq-NSCLC) were observed. Pharmacodynamic biomarkers showed increased TRIB3 and CHOP levels. Conclusions: The combination of ABTL0812+P/C was safe and tolerated, efficacy signals were observed, and biomarker modulation confirmed drug activity. The triple combination is currently being evaluated in both indications in a Phase 2 study. Clinical trial information: NCT03366480

LATEST NEWS

31.05.2019

News

Ability Pharmaceuticals Announces the Presentation of the First Results of ABTL0812 as First Line in Patients with Endometrial or Lung Cancer at 2019 ASCO Annual Meeting + info
04.02.2019

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Ability Pharmaceuticals Announces the Approval in China of a Clinical Study in Pancreatic Cancer with ABTL0812 + info
30.01.2019

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Ability Pharmaceuticals is attending the BIOMED EVENT® by INVEST SECURITIES and the Cholangiocarcinoma Foundation Annual Conference + info
05.12.2018

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AbilityPharma ha superado el millón de euros en la ronda de crowdfunding que abrió el pasado mes de septiembre + info
07.11.2018

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Ability Pharmaceuticals Announces FDA-Orphan Drug Designation for ABTL0812 in Biliary Tract Cancer + info
19.09.2018

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Ability Pharmaceuticals anuncia la inclusión del primer paciente en el estudio clínico de la fase 2 de ABTL0812 en Francia + info
24.08.2018

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At AbilityPharma we are very pleased to announce the start of a crowdfunding campaign through de Capital Cell + info
19.02.2018

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AbilityPharma Announces FDA Approval of Phase 1/2 Trial of ABTL0812 for Patients with Advanced Metastatic Pancreatic Cancer + info
13.12.2017

News

AbilityPharma Announces FDA Approval of IND for Phase 2 Trial of ABTL0812 in Patients with Endometrial Cancer or Squamous Non-Small Cell Lung Cancer + info
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