The FDA has given orphan drug designation to ABTL0812 for the treatment of pancreatic cancer. In preclinical studies, ABTL0812 has shown efficacy in pancreatic cancer as single agent and synergistic effect (by 8 to 90 times) in combination with taxanes, platinum compounds and gemcitabine, with induction of tumor regression without increasing the toxicity associated with chemotherapy.
First-line therapy in patients with either locally advanced or metastatic pancreatic cancer includes these compounds, and administered in combination with ABTL0812 could greatly improve the treatment outcome.
ABTL0812 causes cell death by autophagy through the overexpression of TRIB3, an endogenous Akt regulator. 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 the phase I/Ib clinical trial (29 patients), ABTL0812 showed the best safety and tolerability compared to other inhibitors of the pathway, without dose-limiting toxicities. The efficacy was comparable to the best PI3K/Akt/mTOR inhibitors; two patients had extremely long disease stabilizations (14 and 18 months).
ABTL0812 is currently in phase II as first-line therapy in combination with chemotherapy in patients with endometrial or squamous lung cancer at Vall d'Hebron Institute of Oncology and Catalan Institute of Oncology in Barcelona.