Date: 2016-02-08
Type of information: DSMB assessment
phase: 3
Announcement: DSMB assessment
Company: PharmaMar (Spain)
Product: PM1183 plus doxorubicin
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. PM1183 is currently being investigated in different tumor types, including a Phase 3 study for platinum-resistant ovarian cancer, a Phase 2 study for BRCA1/2-associated metastatic breast cancer and a Phase 1b study for small cell lung cancer.
Disease: ovarian cancer
Therapeutic area: Cancer - Oncology
Country: USA, Europe
Trial
details: This multicenter, open-label, randomized, controlled phase III clinical trial will evaluate the activity and safety of PM01183 versus pegylated liposomal doxorubicin (PLD) or topotecan as control arm in patients with platinum-resistant ovarian cancer. PM01183 will be explored as single agent in the experimental arm (Arm A) versus PLD or topotecan in the control arm (Arm B). (NCT02421588)
Latest
news: * On February 8, 2016, PharmaMar announced that the Independent Data Monitoring Committee (IDMC) has notified the Company of its recommendation that the Phase III (CORAIL) trial currently under way with PM1183 * On June 29th, 2015, PharmaMar announced the start of a phase III study for PM1183 in patients with platinum-resistant ovarian cancer (PROC). Once study objectives are met, the CORAIL trial will be used to support the regulatory filing of PM1183 as treatment for this indication.The pivotal study is a randomized, open-label, and international multicenter trial designed to evaluate the activity and safety of PM1183 compared with investigator´s choice of topotecan or pegylated liposomal doxorubicin (PLD) in patients with PROC. Enrolling a total of 420 women with unresectable disease across more than 100 medical centers in the US and Europe, the CORAIL trial will assess whether PM1183 can improve progression-free survival, as primary endpoint, compared to topotecan and PLD, which are currently approved for ovarian cancer in second-line treatment. Secondary outcome measures include assessing overall survival, overall response rate and patient-reported quality of life. Data from the preceding phase II trial in these patients showed a progression-free survival of 5.7 months, which was significantly better compared to the 1.7 months achieved by patients treated with topotecan.
in platinum-resistant ovarian cancer patients should continue without any changes. The IDMC's recommendation came after an analysis of the safety data obtained with the first 80 patients treated in the trial. This pivotal randomised Phase III trial assesses the efficacy of PM1183 compared with the standard treatment for this
indication—topotecan or pegylated liposomal doxorubicin—in a total of 420 patients.
