Date: 2016-10-10
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2016 Congress
Company: PharmaMar (Spain)
Product: PM01183 (lurbinectidin)
Action
mechanism: transcriptional inhibitor. PM01183 is a novel synthetic marine-derived compound that covalently binds to the minor groove of the DNA. These PM01183-DNA adducts give rise to double strand breaks and perturbations of the cell cycle inducing cell death. PM01183 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.
Disease: breast cancer
Therapeutic area: Cancer - Oncology
Country: Spain, USA
Trial details:
Latest
news: * On October 10th , 2016.- PharmaMar announced the positive results of its Phase II study of lurbinectedin (PM1183) in patients with BRCA 1 / 2 – associated metastatic breast cancer, who had previously received a maximum of 3 prior chemotherapy regimens. Doctor Judith Balmaña, oncology expert from the Vall D´Hebron Institute of Oncology, and principal investigator of the trial, presented the data at an oral session at the European Society of Medical Oncology (ESMO) Congress, being held in Copenhagen. The primary endpoint of the trial is to analyze the antitumoral activity of lurbinectedin in this cohort of patients in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST V1.1). 54 patients were treated in total and a significant reduction in tumor size was observed in 22 of them (ORR 41%). The primary endpoint of at least 17 responses was comfortably achieved. It is important to emphasize that the ORR of the patients 2 with BRCA 2 gene mutation subgroup was 61%, while in those patients with BRCA 1 gene mutation, the figure was 26%. Apart from this parameter, others, such us median duration of response (6.7 months), progression free survival (4.1 months), one year overall survival (15.9 months), and clinical benefit (reduction in tumor lesions, or at least 3 months stability) in 61% of patients were observed. Throughout the clinical trial, the 7 mg initial dose of lurbinectedin was adjusted to 3.5 mg/m2 , both being administered intravenously every three weeks with the objective of improving the safety profile of the drug. The investigator´s team, led by Dr Balmaña, arrived to the conclusion that lurbinectedin (PM1183) is an active compound in BRCA associated metastatic breast cancer, even independently of the prior treatment with platinum. With the dose adjustment to 3.5 mg/m2 , the tolerance to the drug was significantly improved, while the compound´s efficacy was maintained. PharmaMar will continue with the clinical development of this molecule in patients with this type of metastatic cancer, given the clinical results obtained in this Phase II study. On July 2 2012, After launching Phase II trials in pancreatic and platinumresistant ovarian cancer, PharmaMar is commencing a Phase II trial with its PM01183 compound in breast cancer. The endpoint is to evaluate the compound's antitumour activity as second- to fourth-line treatment in patients with this illness. At least 50 (first phase) and at most 117 evaluable patients will be treated in the hospitals participating in this important trial.
