Date: 2015-06-02
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Janssen Research & Development, a J&J company (USA - NJ) Pharmamar (Spain)
Product: Yondelis® (trabectedin )
Action
mechanism: transcriptional inhibitor. Yondelis® (trabectedin) is a novel, synthetically produced antitumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. The drug exerts its activity by targeting the transcriptional machinery. It is approved in 81 countries in North America, Europe, South America and Asia for the treatment of advanced soft tissue sarcomas as a single-agent and for relapsed ovarian cancer in combination with Doxil®/Caelyx® (doxorubicin HCl liposome injection). Under a licensing agreement with PharmaMar, Janssen Products, L.P. has the rights to develop and sell Yondelis® globally except in Europe, where PharmaMar holds the rights, and in Japan, where PharmaMar has granted a license to Taiho Pharmaceuticals. Trabectedin is approved in 77 countries in North America, Europe, South America and Asia under the tradename Yondelis® for the treatment of advanced STS as a single-agent. Janssen submitted a New Drug Application for Yondelis® to the FDA on November 24, 2014, which was granted a Priority Review on February 3, 2015.
Disease: advanced liposarcoma or leiomyosarcoma
Therapeutic area: Cancer - Oncology
Country: Australia, Brazil, New Zealand, South Africa, USA
Trial
details: This randomized study is an open-label, active-controlled, parallel-group, multicenter phase 3 study. This study will be divided into 3 phases, screening, treatment, follow-up and optional extension phase (OEP). During screening, potential participants will be assessed for study eligibility after providing signed informed consent. Approximately 570 patients will be randomly assigned in a 2:1 ratio to either the trabectedin (n=380) or dacarbazine (n=190) treatment groups. During the treatment phase, patients will receive study drug once every 3 weeks, until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1 criteria) or signs of toxicity. Assessments will be performed to evaluate the effectiveness of the drug, and patient safety will be monitored. (NCT01343277)
Latest
news: * On June 2, 2015, PharmaMar communicated that Janssen Research & Development, LLC (Janssen) announced data from the Phase 3 multicenter study SAR3007, which demonstrated a significant improvement in progression-free survival (PFS) with trabectedin (Yondelis®) compared to dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) previously treated with an anthracycline and at least one additional chemotherapy regimen. SAR3007 is the largest randomized Phase 3 study ever conducted in this patient population. These data were presented in an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. (Abstract 10503)
In this randomized, active-controlled Phase 3 study in patients with advanced LPS or LMS, trabectedin significantly reduced the risk of disease progression or death by 45 percent compared with those who received dacarbazine (hazard ratio [HR] = 0.550; P< 0.0001; median [M] 4.2 vs 1.5 months, respectively), with results validated through an audit by independent radiologists. The improved PFS benefit with trabectedin treatment was consistently observed across all clinically relevant subgroups and was further supported by an increased objective response rate, a longer duration of response, and a higher clinical benefit response rate as compared to dacarbazine. At the interim analysis for overall survival (OS), the trial had not met the primary endpoint of OS and the study is ongoing to determine the final OS results, which will be presented at a future meeting. The results for the secondary efficacy endpoints are mature.
Safety findings were consistent with the well-characterized safety profiles of both agents, with the most common Grade 3-4 toxicities in the trabectedin versus the dacarbazine groups being decreased absolute neutrophil count (40% vs. 25%), decreased platelets (19% vs. 20%), and transient increases in liver transaminases, including alanine transaminase (ALT) (29% vs. 1%). Drug-related deaths occurred in 2.1% of patients in the trabectedin group versus 0% of patients in the dacarbazine group.
The Phase 3 multicenter study SAR3007 compared trabectedin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) previously treated with an anthracycline and at least one additional chemotherapy regimen. The primary endpoint is overall survival (OS) and secondary endpoints included progression-free survival (PFS), time to progression (TTP), objective response rate (ORR), duration of response (DOR), symptom severity and safety. Both treatments were administered via an IV infusion every three weeks with the trabectedin dose of 1.5 mg/m2 given over 24 hours versus dacarbazine dose of 1 g/m2 given over 20-120 min. Ninety-four percent of study participants were in the U.S.
