Date: 2016-05-20
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: PharmaMar (Spain)
Product: lurbinectedin (PM1183) in combination with irinotecan
Action
mechanism: transcriptional inhibitor/RNA polymerase II inhibitor. Lurbinectedin is an inhibitor of RNA polymerase II. This synthetic marine-derived compound covalently binds to the minor groove of the DNA. These lurbinectedin-DNA adducts give rise to double strand breaks and perturbations of the cell cycle inducing cell death. Lurbinectedin induces a specific degradation in tumour cells of RNA polymerase II, without interfering other RNA polymerases (I and III)-the degradation depends on whether the transcription process is active (transactivated transcription) and does not affect basal transcription. In preclinical trials, the compound evidenced strong activity against tumour cell lines of different origins. The antitumor efficacy of lurbinectedin is being investigated in various types of solid tumors, including a Phase III study for platinum-resistant ovarian cancer, a Phase II study for BRCA 1 and BRCA 2- associated metastatic breast cancer and a Phase III study for small cell lung cancer.
Disease: advanced solid tumors
Therapeutic area: Cancer - Oncology
Country:
Trial
details: This prospective, open-label, dose-ranging, uncontrolled Phase I study has the objective of analyzing the safety profile, along with the handling of lurbinectedin and irinotecan in the study population. It also aims to characterize the pharmacokinetics (PK); to obtain preliminary information on the antitumoral activity of this combination and to evaluate the pharmacogenomics with tumor samples from patients exposed to both compounds in order to assess potential markers to both response and/or resistance.
Latest
news: * On May 20, 2016, PharmaMar has announced the beginning of an open-label, multicenter, Phase I study to evaluate the Maximum Tolerated Dose (MTD) and the Recommended Dose (RD) of lurbinectedin (PM1183) in combination with irinotecan, in patients with selected, advanced solid tumors. Dr Arturo Soto, Director of the Clinical Department of PharmaMar´s Oncology Business Unit, explains “four investigation centers from the US and Europe will participate. The number of patients to be included in the study will depend on the tolerability to the combination of drugs and also on the number of doses that will be needed to reach the MTD. We expect around one hundred patients to be treated with lurbinectedin in combination with irinotecan”.
