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Ref Type Journal Article
PMID (30089585)
Authors Cho BC, Dy GK, Govindan R, Kim DW, Pennell NA, Zalcman G, Besse B, Kim JH, Koca G, Rajagopalan P, Langer S, Ocker M, Nogai H, Barlesi F
Title Phase Ib/II study of the pan-cyclin-dependent kinase inhibitor roniciclib in combination with chemotherapy in patients with extensive-disease small-cell lung cancer.
Journal Lung cancer (Amsterdam, Netherlands)
Vol 123
Issue
Date 2018 Sep
URL
Abstract Text This phase Ib/II study evaluated safety, pharmacokinetics, maximum tolerated dose (MTD), and efficacy of the pan-cyclin-dependent kinase inhibitor roniciclib with cisplatin-etoposide (CIS-ETOP) or carboplatin-etoposide (CARBO-ETOP) in patients with extensive-disease small-cell lung cancer (ED-SCLC).In this open-label, non-randomized study, patients with previously untreated ED-SCLC received roniciclib twice daily (BID) in a 3 days on/4 days off schedule. Cisplatin 75 mg/m2 or carboplatin (AUC5) dose was administered on day 1, and etoposide 100 mg/m2 on days 1-3, of 21-day cycles. Phase Ib used a dose-escalation design to define the MTD for phase II. Pharmacokinetics were assessed.Forty-three patients received treatment (roniciclib 2.5 mg BID [+ CARBO-ETOP, n = 4; + CIS-ETOP, n = 3] and roniciclib 5 mg BID [+ CARBO-ETOP, n = 24; + CIS-ETOP, n = 12]). The MTD of roniciclib was 5 mg BID with CARBO-ETOP or CIS-ETOP. Common adverse events were nausea (90.7%) and vomiting (69.8%). Roniciclib was readily absorbed following oral administration at the MTD (median tmax 0.5-1 h), with a 30-40% reduction in exposure when co-administered with CARBO-ETOP or CIS-ETOP; administration of roniciclib had no effect on etoposide or platinum pharmacokinetics. The response rate was 81.4% (35/43) overall and 86.1% (31/36) in the pooled roniciclib 5 mg BID population (all partial responses).Roniciclib co-administered with chemotherapy in patients with ED-SCLC demonstrated tolerability, acceptable pharmacokinetics, and promising efficacy. An observed safety signal in a related phase II study resulted in discontinuation of the present study and termination of further roniciclib development.

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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 lung small cell carcinoma not applicable Carboplatin + Etoposide + Roniciclib Phase Ib/II Actionable In a Phase Ib/II trial, first-line treatment with the combination of Roniciclib (BAY1000394) and either carboplatin plus etoposide or cisplatin plus etoposide demonstrated tolerability and resulted in a response rate of 81.4% (35/43; all partial responses), median OS of 12.6 mo, and median PFS of 7.3 mo in extensive disease small cell lung cancer patients; however due to a safety signal in a related trial further development of Roniciclib (BAY1000394) was discontinued (PMID: 30089585; NCT01573338). 30089585