At ESMO 2021 the company announced new preliminary clinical data from the 6mg cohort of its ongoing Phase II ACCURACY trial of AL101 for the treatment of recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch-activating mutations.
Adenoid Cystic Carcinoma (ACC) is a rare form of cancer that generally develops in the salivary glands or other region of the head and neck. The patients with notch mutations have a more aggressive form of cancer. ACC is an immunologically “cold” tumor that is refractory to chemotherapy, with a recurrence rate of about 60% after initial surgery. AL101 is a gamma secretase inhibitor (GSI) that selectively inhibits notch 1,2,3, and 4. The FDA has granted Fast-Track and Orphan drug designation to AL101 for the treatment of ACC. The company is testing the drug in two phase II trials ACCURACY and TENACITY, in patients with ACC and triple negative breast cancer (TNBC), respectively. Previously, the company has also done preclinical of AL101 in combination with approved therapies and it has demonstrated significant tumor growth inhibition, including regressions, compared to each drug alone paving way for a possible future combination.
In the 6mg cohort of ACCURACY trial 42 patients were enrolled. The disease control rate (DCR) of 70% was observed, which includes partial responses of 9% plus stable disease observation of 61%. The disease progression was observed in 24% of patients.
“ACC is an orphan disease with no approved therapies and patients with Notch mutations have a more aggressive disease course and poorer survival outcomes as compared to patients with Notch wild-type. R/M ACC remains a significant area of unmet need, and I am encouraged by the preliminary results that AL101 monotherapy has demonstrated to-date. Coupled with new preclinical data showing that AL101 in combination with approved targeted therapies could potentially treat a greater proportion of ACC tumors, regardless of Notch mutations.
On the safety front the drug was well tolerated with manageable side effects consistent with those observed in the 4mg QW cohort with no new adverse events (AEs) specific to the 6mg cohort. The serious TRAEs were reported in 31% of patients.
“The preliminary safety and efficacy data from the 6mg cohort of our ongoing ACCURACY trial of AL101 highlights a favourable profile. We are pleased to see that AL101’s safety profile continues to be tolerable and manageable, providing us with potential dosing flexibility as we continue to advance our development plans. We continue to see strong potential for AL101 to transform the treatment landscape for R/M ACC patients with Notch mutations and we look forward to reporting additional clinical data in 2022.”
— Chief Medical Officer of Ayala
INSIGHTS: We are excited to see how AL101 may be developed as a viable treatment option for R/M ACC patients. While these results are still preliminary, the safety profile of AL101 and the disease control rate of 70% are promising indicators. ACC accounts for 10% of salivary gland tumor and it has no approved treatment, which makes the disease management difficult. Elevar Therapeutics’ Rivoceranib (tyrosine kinase inhibitor) is another orphan designated drug in the race for ACC, which can create a competition in the already barren market. The current result looks good but additional data in 2022 will give more visibility, hence, the combination with approved therapies will further enhance the ACC drugs market along with Head and Neck cancers in the future.