A phase 1/2 trial (NCT04892017) found a potential treatment with DCC-3116 monotherapy given between 50 mg to 300 mg twice daily for patients with RAS or RAF-mutant solid tumors, based on a presentation from the 2022 European Society for Medical Oncology Congress.
At the June 9, 2022, data cutoff, no dose-limiting toxicities or serious treatment-emergent adverse effects (TEAEs) were reported. Additionally, the disease control rate at week 16 was 29% among 14 response-evaluable patients, with the best overall response being stable disease.
In the 18-patient safety population, the most common TEAEs of any grade included fatigue (39%), dehydration (22%), increased alanine transaminase (ALT; 17%), and anemia (17%). No grade 4 TEAEs or deaths related to DCC-3116 were reported. There were 2 instances of asymptomatic, reversible increased ALT of grade 3 that led to a dose interruption and a dose reduction, respectively.
“DCC-3116 is a first-in-class, potent, and selective small molecule switch-control kinase inhibitor of ULK1/2,” Anthony W. Tolcher, MD, a medical oncologist at Texas Oncology-San Antonio Babcock Next Oncology, said during the presentation. “In preclinical models, it potently inhibits the proximal substrates ATG13 and ATG14 and blocks autophagy. In preclinical studies, when it is combined with a number of different MAP kinase pathway inhibitors, it leads to either additive or synergistic antitumor activity.”