ABX196 for Hepatocellular Carcinoma
ABX196 has been developed as a synthetic agonist of iNKT cells from a proprietary platform technology that identifies agonists of these types of cells that demonstrate immune enhancing effects in cancer models.
Preclinical data showed that ABX196 enhanced anti-tumoral activity when used alone and in combination with anti-PD1 antibodies or doxorubicin.
ABX196 was selected for development because of its ability to direct the immune system towards tumors that respond sub-optimally to anti-PD1 antibodies and has demonstrated in mouse models an ability to potentiate the anti-tumoral response to chemotherapy.
A Phase 1 clinical trial in healthy volunteers has been completed and showed safety and activation of iNKT cells. Further immuno-oncology preclinical studies demonstrated the potential of the product in oncology, in particular in turning tumors not responsive to anti-PD1 (cold) to tumors responsive to anti-PD1 (hot).
In the Clinic
Abivax is currently running a Phase 1/2 clinical trial, where hepatocellular carcinoma (HCC) patients are treated with ABX196 in combination with the checkpoint inhibitor nivolumab (Opdivo®, Bristol Myers Squibb). This trial is conducted in collaboration with the Scripps MD Anderson Cancer Center in San Diego and the MD Anderson Cancer Center in Houston. The IND was granted by the U.S. authority, the FDA, in May 2019, and the first patient was treated with ABX196 in combination with nivolumab in February 2020.
In January 2022, the results of the dose escalation phase of this phase 1/2 study were presented at the ASCO GI Cancers Symposium. 10 patients were enrolled and dosed with 0.1µg, 0.2µg, or 0.4µg ABX196 in combination with nivolumab. Key objectives were to assess safety, maximum tolerated dose as well as signs of clinical benefit. A clinical benefit was observed in 5 patients, including 1 patient with a partial response and 4 patients with stable disease. Median progression-free survival for all patients was 113.5 days (49-450 days) and at 276 days (172-450 days) for those showing a clinical benefit.
Based on the first outcome, Abivax is currently evaluating the design of a follow-on study of ABX196 in HCC and, in parallel, assessing potential partnering options.