Discussion
toxicity, cancer, SD
CANCER, SOLID TUMORS
An oral PIC formulation of the CDC7-selective small molecule inhibitor, TAK-931, has been evaluated in phase 1/2 clinical trials (NCT02699749 [Considering the potential mechanisms of action of TAK-931 (interfering with DNA repair and replication, and subsequently inducing apoptosis in cancer cell lines [The safety analysis indicated that treatment with TAK-931 was well tolerated, with an acceptable toxicity profile. TEAEs were most commonly gastrointestinal in nature, consistent with those previously reported in the first-in-human phase 1 study [TAK-931 activity was not evident in this cohort of patients with locally advanced or metastatic solid tumors. These results are not consistent with the antitumor activity reported in the first-in-human phase 1 study, in which 4 of 24 response-evaluable patients had prolonged SD and 3 experienced a partial response [In conclusion, the PKs and systemic exposures of TAK-931 were similar following administration of the tablet and PIC formulations. The PK and safety results support the transition from PIC to the tablet formulation, which will facilitate the clinical development of TAK-931.