9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. It acts through downregulation of NF-κB and decreases the expression NF-κB target genes cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. 9-ING-41 may also function as an immune modulatory agent by decreasing checkpoint expression and enhancement of T-cell / NK-cell effector function. This is a phase 2, open-label, non-randomized, single institution study investigating the novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). The safety of this combination has been established in the Actuate 1801 study. Thirty-one evaluable patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.~The primary aim of the study is to assess the overall response rate (ORR) as defined by RECIST v1.1 in the overall study population (including both Cohorts 1 and 2). Secondary aims include assessing progression-free survival (PFS), overall survival (OS), determining safety and tolerability, measuring patient-reported quality of life metrics, and correlating efficacy with molecular and immunologic predictors of response. We hypothesize that the novel combination of a GSK-3β inhibitor with carboplatin chemotherapy will result in an ORR of 25% or greater in this patient population where no approved therapies have been established.
9-ING-41 is a small molecule potent selective GSK-3β inhibitor with antitumor activity. This study investigates 9-ING-41 in combination with carboplatin chemotherapy in patients with incurable, recurrent or metastatic salivary gland carcinomas (SGC). Patients with advanced SGC (including all histologic subtypes and adenoid cystic carcinoma [ACC]) will receive 9-ING-41 intravenously (IV) along with carboplatin IV at standard dosing together on Day 1, and 9-ING-41 alone on Day 4 of a 21-day cycle. Participants will be enrolled to two histologic cohorts: Cohort 1 will be comprised of those with ACC, and Cohort 2 will include patients with non-ACC SGC (or all other salivary gland cancer histologies). Treatment will continue until progression of disease, death, or discontinuation of therapy for any reason.