Deciphera Pharmaceuticals, Inc. announced positive initial data from the single agent dose escalation portion of the Phase 1 study of DCC-3116, the Company's first-in-class, potent, and selective small molecule switch-control kinase inhibitor of ULK1/2, in patients with advanced or metastatic tumors with a mutant RAS or RAF gene. Results from the study were presented in an oral presentation as a Proffered Paper titled Initial monotherapy results of a phase 1 first-in-human study of ULK1/2 inhibitor DCC-3116 alone and in combination with MAPK pathway inhibition at the ESMO Congress 2022. As of June 9, 2022, 18 patients with locally advanced or metastatic cancer with a RAF or RAS mutation were enrolled across four cohorts dosed with DCC-3116 twice daily (BID): 50 mg BID (n=3); 100 mg BID (n=4); 200 mg BID (n=7); and 300 mg BID (n=4).
The median number of prior anti-cancer regimens was three (range 1-10). The most common cancer types were colorectal (56%) and pancreatic (28%) and patients had KRAS (83%) and BRAF (17%) mutations. The results of the primary objectives of safety and tolerability as well as the additional objectives of pharmacokinetics, pharmacodynamics, and anti-tumor activity are summarized below: Treatment with DCC-3116 was well tolerated and most treatment-emergent adverse events (TEAEs) were Grade 1/2; the most common (=15%) TEAEs regardless of relatedness reported (all grades) were: fatigue (39%), dehydration (22%), alanine transaminase (ALT) increases (17%), anemia (17%), aspartate transaminase (AST) increases (17%), decreased appetite (17%), hyponatremia (17%), nausea (17%), and vomiting (17%).
No dose-limiting toxicities or treatment-related serious adverse events were observed with DCC-3116; two asymptomatic, reversible Grade 3 alanine transaminase increases that led to dose interruption and reduction were reported as treatment-related.