Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity

Summary: Background This trial evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and activity of volasertib, a selective Polo-like kinase 1 inhibitor that induces mitotic arrest and apoptosis, combined with cisplatin or carboplatin in patients with advanced/metastatic solid tumors (NCT00969761; 1230.6). Methods Sequential patient cohorts (3+3 dose-escalation design) received a single infusion of volasertib (100-350 mg) with cisplatin (60-100 mg/m2) or carboplatin (area under the concentration versus time curve [AUC]4-AUC6) on day 1 every 3 weeks for up to six cycles. Sixty-one patients received volasertib/cisplatin (n=30) or volasertib/carboplatin (n=31) for a median of 3.5 (range, 1-6) and 2.0 (range, 1-6) treatment cycles, respectively. Results The most common cycle 1 dose-limiting toxicities (DLTs) were thrombocytopenia, neutropenia and fatigue. MTDs (based on cycle 1 DLTs) were determined to be volasertib 300 mg plus cisplatin 100 mg/m2 and volasertib 300 mg plus carboplatin AUC6. Co-administration did not affect the pharmacokinetics of each drug. Partial responses were observed in two patients in each arm. Stable disease was achieved in 11 and six patients treated with volasertib/cisplatin and volasertib/carboplatin, respectively. Conclusions Volasertib plus cisplatin or carboplatin at full single-agent doses was generally manageable and demonstrated activity in heavily pretreated patients with advanced solid tumors.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase I trial of volasertib (BI 6727), a polo-like kinase 1 (Plk1) inhibitor, in combination with cisplatin or carboplatin in patients with advanced solid tumors.

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Phase I safety and pharmacokinetic dose-escalation study of pilaralisib polymorph E, a phosphoinositide 3-kinase inhibitor in tablet formulation, in patients with solid tumors or lymphoma

Pilaralisib (SAR245408), a pan-class I PI3K inhibitor, has been investigated in Phase I/II trials in several solid tumors and lymphomas in capsule and tablet formulations of polymorph A (capsule-A and tablet-A). This Phase I study was conducted to determine the recommended Phase II dose (RP2D) of a more thermodynamically stable form of pilaralisib (polymorph E), in tablet formulation (tablet-E), in patients with advanced solid tumors or relapsed/refractory lymphoma.status: publishe