Abivertinib, discovered by ACEA Therapeutics (a subsidiary of Sorrento Therapeutics), is a dual inhibitor of the epidermal growth factor receptor (EGFR) and Bruton’s Tyrosine Kinase (BTK) receptor.
As a third-generation EGFR inhibitor for NSCLC, Abivertinib has three advantages: the inhibition of T790M isoform-specific kinase activity, maintaining efficacy against exon 19 and 21 mutations, and sparing the inhibition of wild-type EGFR. More than 600 patients have been treated with Abivertinib at different doses. Favorable clinical efficacy and manageable adverse events in 300 patients with EGFR T790M+ NSCLC as a second line therapy was reported in ASCO conference. Abivertinib showed similar efficacy with Osmertinib, an only FDA approved third generation EGFR inhibitor, but a different resistant mechanism, warranting a potential of alternative use in NSCLC (Mol Cancer Ther 15: 2586-2597; EBioMedicine 43:180-187; Neoplasia 41: 41-51; Sci. Bull. 64:499-503). Abivertinib phase III study as first line therapy for NSCLC has been launched in China.
Abivertinib is also a potent irreversible inhibitor of BTK which is a critical molecule in B cell development and signaling. Abivertinib is being investigated in an open-label phase I study in patients with R/R B–cell lymphoma (NCT03060850). Favorable safety and tolerability with encouraging clinical efficacy in patients with R/R B-cell malignancies, a phase II registration trial with a subtype B-cell lymphoma will be soon initiated.
BTK is also a critical molecule in immune regulation and host inflammatory responses. Abiveritinib showed potent anti-inflammation and immune modulation activities by inhibiting production of key pro- inflammatory cytokines including IL-1beta, IL-6 and TNF-alpha. These cytokines are associated with cytokine release syndrome (CRS) and COVID-19 disease progression with poor outcomes in patients with acute respiratory distress syndrome (ARDS). The trial, titled A Phase 2, Double Blinded, Randomized Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) With Standard of Care Versus Standard of Care in Subjects Hospitalized With COVID-19 (NCT04440007), will be initially conducted in centers in the USA.
Investigator Initiated Trials (IIT)
We believe in supporting healthcare providers via Investigator Initiated Trials (IIT) to improve the medical and scientific knowledge of our compounds in clinical development. An IIT may be a clinical or non-clinical study for which ACEA provides funding and/or drug compound. For clinical studies, our focus is on trials that evaluate abivertinib in adults with solid tumors or blood cancer as a stand-alone agent or in combination therapy regimens (requests outside of this area will not be considered at this time).
We believe in supporting healthcare providers through Investigator Initiated Trials (IIT).
We support IITs that will:
- Contribute knowledge to the medical and scientific community
- Address unmet needs of patients and their healthcare providers
- Have outcomes communicated in an appropriate scientific forum, including peer-reviewed publications
Examples of appropriate requestors of IIT support include, but are not limited to:
- Healthcare providers and their institutions
- Members of the scientific community and their institutions (colleges and universities)
- Government research institutions
If you are interested in evaluating abivertinib or any of our other pipeline compounds for potential use in the treatment of cancer or autoimmune disease, please contact us at ACEA-IIT@aceatherapeutics.com.