Ability Pharmaceuticals announced the United States Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application which allows AbilityPharma to proceed with a phase 1/2a clinical trial of ABTL0812, its autophagy inducer via PI3K/Akt/mTOR pathway inhibition, in patients with endometrial cancer or squamous non-small cell lung cancer, in combination with paclitaxel and carboplatin as first-line therapy. AbilityPharma submitted its IND on October 31, 2017.
The trial is ongoing in Europe, where a total of 80 patients will be enrolled. Since November 2016, patients are being included in Vall d'Hebron Institute of Oncology VHIO (Barcelona), Institut Català d'Oncologia ICO (L'Hospilatet, Badalona and Girona in Catalonia), INCLIVA (València) and Hospital Universitario Virgen del Rocío (Sevilla). In early 2018 the trial will start recruiting patients in Institut Gustave Roussy (Paris), Centre Léon Bérard (Lyon) and Institut Paoli-Calmettes (Marseille), following the Clinical Trial Application (CTA) approval in France in October 2017.
"After this major achievement, we are continuing with enthusiasm the preparations of additional INDs and CTAs with new clinical trials in both Europe and the US,” Gemma Fierro, Vice President of Clinical and Regulatory Affairs of AbilityPharma, said.
ABTL0812 causes autophagy-mediated cell death through the overexpression of TRIB3, a protein regulating Akt. It is a first-in-class, fully differentiated oral targeted anticancer compound inhibiting the PI3K/Akt/mTOR pathway without being a direct kinase inhibitor.
In preclinical cancer models ABTL0812 is efficacious as single agent with outstanding safety profile in a broad spectrum of cancer types. It also has synergistic effect with chemotherapy without increasing its toxicity.
In phase 1, ABTL0812 had excellent safety and tolerability compared to other inhibitors of the pathway, without dose-limiting toxicities. Two patients had extremely long disease stabilizations over one year (14 and 18 months). Additionally, ABTL0812 showed high efficacy on biomarkers of the pathway, with dose-response effect.