bay-1000394 and Fatigue

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D).. Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway.. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6).. Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cyclin-Dependent Kinases; Diarrhea; Fatigue; Female; Gene Expression; Humans; Lung Neoplasms; Lymphoma; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neoplasms; Ovarian Neoplasms; Proliferating Cell Nuclear Antigen; Pyrimidines; Signal Transduction; Small Cell Lung Carcinoma; Sulfoxides; Vomiting