Announced today by Catalan biopharmaceutical company, Ability Pharmaceuticals SL, VHIO has been selected to lead a phase II clinical trial aimed at testing the safety and efficacy of novel targeted therapy ABTL0812 in combination with a duo of chemotherapeutics — paclitaxel and carboplatin, as first line treatment of patients with advanced or recurrent endometrial cancer.
Having shown early promise in a phase Ib study, evidencing improved tolerability and greater efficacy compared with other inhibitors of the P13K/Akt/mTOR pathway – a pivotal player in many human cancers, this agent could ultimately represent a critical and new therapeutic avenue for these patients who have unfortunately ceased to respond to other anti-cancer therapies.
To be carried out across sites in Spain and France, Ana Oaknin, Principal Investigator of VHIO´s Gynecological Malignancies Group, in collaboration with Jordi Rodón, Principal Investigator of VHIO´s Early Clinical Drug Development Group and Director of its Research Unit for Molecular Therapy of Cancer (UITM) – “la Caixa”, will spearhead research focused on endometrial cancer, and Ernest Nadal from the Catalan Institute of Oncology (ICO) will lead the study in patients with squamous lung cancer.
For more on this Phase II clinical trial please see Ability Pharmaceuticals´ recent announcement below:
Source: Ability Pharmaceuticals, SL
Ability Pharmaceuticals Initiates Phase 2 Combination Trial with ABTL0812 as First Line Therapy in Patients with Endometrial or Squamous Lung Cancer
• ABTL0812 is administered in combination with carboplatin and paclitaxel
• Vall d’Hebron Institute of Oncology (VHIO, Barcelona) and Catalan Institute of Oncology (ICO, L’Hospitalet, Barcelona) lead the study, which includes other centers in Spain and France
BARCELONA, Catalonia, Spain – November 22, 2016. The Catalan biopharmaceutical company Ability Pharmaceuticals, SL announced today the initiation of its first Phase 2 Clinical Trial with its novel targeted anticancer agent ABTL0812 to evaluate its efficacy and safety in combination with paclitaxel and carboplatin in 80 patients with advanced or recurrent endometrial cancer or squamous lung cancer as first-line therapy. The study will be conducted in Spain and France with Dr. Ana Oaknin at Vall d’Hebron Institute of Oncology (VHIO, Barcelona) as principal investigator for endometrial cancer and Dr. Ernest Nadal at Institut Català d’Oncologia (ICO, Hospitalet-Barcelona) as principal investigator for lung cancer. Dr. Jordi Rodon (also from VHIO) is the coordinating investigator.
Dr. Carles Domènech, Chief Executive Officer and co-founder of AbilityPharma, said: “We are very happy to have reached this important development milestone. We face with enthusiasm taking to clinical proof of concept a new important product to treat cancer patients, especially as first line choice in squamous lung cancer and endometrial cancer, clear unmet medical needs”.
“ABTL0812 has shown to be an extremely safe compound in patients during the Phase 1b with initial clinical efficacy and high activity on biomarkers”, said Dr. José Alfón, Vice-President of Research and Development at AbilityPharma. “Additionally, the high efficacy and safety observed in combination in preclinical models make us expect good results in the phase 2 trial”.
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. Its unique mechanism of action was published at Clinical Cancer Research in 2015.
In preclinical cancer models ABTL0812 is efficacious as single agent with an excellent safety profile in a broad spectrum of cancer types: lung, endometrial, pancreatic cancer and neuroblastoma. In these models the compound has also synergistic effect with chemotherapy (taxanes, platinum compounds and gemcitabine) without increasing its toxicity. ABTL0812 is also active on cells resistant to chemotherapy or other targeted therapies, on tumor stem cells and inhibits metastasis formation. Preliminary results show promising immunomodulatory effects.
In the phase 1/1b clinical trial (29 patients with advanced solid tumors), ABTL0812 showed the best safety and tolerability compared to other inhibitors of the pathway; no dose-limiting toxicities were identified. The efficacy in patients was comparable to the best PI3K/Akt/mTOR inhibitors in similar clinical trials. Remarkably 2 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. Due to its extremely high safety the recommended phase 2 dose was determined by pharmacokinetic-pharmadynamic modeling.
ABTL0812 has Orphan Drug Status from US FDA and from Europe EMA for the pediatric cancer neuroblastoma.