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|Ref Type||Journal Article|
|Authors||Bahleda R, Grilley-Olson JE, Govindan R, Barlesi F, Greillier L, Perol M, Ray-Coquard I, Strumberg D, Schultheis B, Dy GK, Zalcman G, Weiss GJ, Walter AO, Kornacker M, Rajagopalan P, Henderson D, Nogai H, Ocker M, Soria JC|
|Title||Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.|
|Journal||British journal of cancer|
|Date||2017 Jun 06|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||Roniciclib||Phase I||Actionable||In a Phase I trial, treatment with Roniciclib (BAY 1000394) on a 3 days on/4 days off dosing schedule demonstrated safety and resulted in a disease control rate of 32.7% (34/104), with a response rate of 1% (1/104; 1 partial response) and stable disease in 31.7% (33/104) of patients with advanced solid tumors (PMID: 28463960; NCT01188252).||detail... 28463960|
|Unknown unknown||ovarian cancer||not applicable||Roniciclib||Phase I||Actionable||In a Phase I trial, treatment with Roniciclib (BAY 1000394) at the RP2D reduced PCNA expression and resulted in a disease control rate of 40.9% (n=22) in patients with ovarian cancer (PMID: 28463960; NCT01188252).||28463960|
|Unknown unknown||lung small cell carcinoma||not applicable||Roniciclib||Phase I||Actionable||In a Phase I trial, treatment with Roniciclib (BAY 1000394) at the RP2D reduced PCNA expression and resulted in a disease control rate of 17.4% (n=23) in patients with small cell lung cancer (PMID: 28463960; NCT01188252).||28463960|