IBRILATAZAR (ABTL0812) from AbilityPharma increases chemotherapy efectiveness by 40% in patients with endometrial cancer
Ibrilatazar is an oral drug with a novel mechanism of acton that induces autophagy through the inducton of ER-stress and the inhibiton of the PI3K/Akt/mTOR pathway, which is crucial for cellular functon and is implicated in this cancer type.
AbilityPharma, a clinical stage biopharmaceutical company specializing in the development of innovative oncology therapies, today announced that the final data of its Phase 1/2 ENDOLUNG trial evaluating ibrilatazar (ABTL0812) in combination with chemotherapy (paclitaxel/carboplatin) for patients with advanced or recurrent endometrial cancer has been published in BMC Cancer.
The trial benefited from the contribution of global key opinion leaders from select hospitals in Spain and France, including the Vall d'Hebron Institute of Oncology (VHIO) in Barcelona, Gustave Roussy in Paris, Clinic University Hospital in Valencia, Centre Léon Bérard in Lyon, Virgen del Rocío University Hospital in Seville, Paoli-Calmettes Institute in Marseille and the Catalan Institute of Oncology (ICO) in Badalona, l’Hospitalet and Girona.
This significant publication builds upon AbilityPharma’s previous groundbreaking translational research, which was featured in Gynecologic Oncology. These advancements further establish the company’s leadership in the development of autophagy-mediated oncology drugs.
Dr. Carles Domènech, AbilityPharma’s CEO & Co-Founder, stated, “This publication represents a crucial development in the study of new drugs and combinations for advanced endometrial cancer, marking a significant milestone in AbilityPharma’s mission to deliver transformative treatments to cancer patients”.
The first author of the article is Dr. Alexandra Leary, deputy director of the Department of Clinical Oncology at Gustave Roussy, and the senior authors of the article, with equal contribution, are Dr. Alejandro Pérez-Fidalgo, oncologist at the Clinic University Hospital in Valencia, researcher at the INCLIVA Biomedical Research Institute’s Oncology Department and member of the Biomedical Research Network in Cancer (CIBERONC), and Dr. Ana Oaknin, Group Leader of VHIO's Gynecological Malignancies Group and Head of Gynecologic Tumors Unit, Medical Oncology Department, at the Vall d'Hebron University Hospital.
“The PI3K pathway is almost universally altered in endomettial cancer and thus represents a very interesting target. Ibrilatazar is the first PI3K inhibitor demonstrating encouraging activity and excellent side efect profile in the capsule form now available”, noted Dr. Alexandra Leary of Gustave Roussy.
Dr. Alejandro Pérez-Fidalgo of Clinic University Hospital in Valencia explains that, “ibrilatazar, when administered in combination with chemotherapy and subsequently as maintenance therapy, has shown a median survival of over 9 months in advanced endometrial cancer. These results are highly promising. If confirmed in a randomized study, ibrilatazar could become a treatment alternative for this complex disease.”
Summary of main results reported in the publication
- The combination of ibrilatazar plus CP demonstrated an overall response rate (ORR) of 65.8%, comprising a 13.2% complete response and a 52.6% partial response, with a median duration of response (DOR) of 7.4 months (95% CI: 6.3–10.8 months). The median progression-free survival (PFS) was 9.8 months (95% CI: 6.6–10.6), a 40% increase over historical controls, with event-free rates of 73.3% at 6 months and 24.4% at 1 year. The median overall survival (OS) was 23.6 months (95% CI 6.4-ND), with an event-free rate of 74.9% at 1 year. These results suggest an increased efficacy over reference historical controls where ORR, PFS and OS were 51%, 7.1 months and 20.4 months.The combination of ibrilatazar plus paclitaxel/carboplatin exhibited a good safety profile. ibrilatazar aligned with the safety profile of historical controls and did not introduce additional significant adverse events beyond those associated with CP.
- Pharmacokinetic parameters aligned with target engagement observed in preclinical trials, and blood pharmacodynamic biomarkers indicated sustained target regulation for at least 28 days following the initiation of treatment.