Date: 2017-07-21
Type of
information: Results
phase: 2
Announcement: results
Company: Bayer Healthcare (Germany) MorphoSys (Germany) Immunogen (USA - MA)
Product: anetumab ravtansine (BAY 94-9343)
Action
mechanism:
- antibody drug conjugate (ADC). Anetumab ravtansine (BAY 94-9343), is an antibody-drug conjugate consisting of a human anti-mesothelin antibody conjugated to the maytansinoid tubulin inhibitor DM4 via a disulfide-containing linker (a reducible SPDB linker [N-succinimidyl 4-(2-pyridyldithio)butanoate]) on an average of 3 lysyl. The antibody binds to human mesothelin with high affinity and selectivity, thereby inducing efficient antigen internalization. Upon internalization, the DM4 moiety binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of mesothelin-expressing tumor cells.
- In vitro, anetumab ravtansine has demonstrated potent and selective cytotoxicity of mesothelin-expressing cells with an IC50 of 0.72 nmol/L, without affecting mesothelin-negative or nonproliferating cells.
- In vivo, anetumab ravtansine localizes specifically to mesothelin-positive tumors and inhibited tumor growth in both subcutaneous and orthotopic xenograft models. Furthermore, anetumab ravtansine was able to induce a bystander effect on neighboring mesothelin-negative tumor cells.
Disease: mesothelioma
Therapeutic
area: Cancer - Oncology
Country: Australia, Belgium, Canada, Finland, France, Germany, Italy, Republic of Korea, Netherlands, Poland, Russian Federation, Spain, Turkey, UK, USA
Trial
details:
- The main purpose of the 15743 study is to assess efficacy and safety of anetumab ravtansine versus vinorelbine in progression free survival in patients with stage IV mesothelin overexpressing malignant pleural mesothelioma (MPM). The trial randomized 248 patients in a 2:1 ratio to receive either anetumab ravtansine (6.5 mg/kg intravenously every three weeks) or vinorelbine (30 mg/m2 intravenously every week).
- The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, as well as other indicators of efficacy, such as patient-reported outcomes, objective tumor response rate, duration of response, disease control rate, and durable response rate. Safety and tolerability of patients were also continuously monitored. (NCT02610140)
Latest
news:
- • On July 21, 2017, Bayer announced that a Phase II clinical trial evaluating anetumab ravtansine (BAY 949343) as a monotherapy in patients with recurrent malignant pleural mesothelioma, who were previously treated, did not meet its primary endpoint of progression-free survival. The safety and tolerability of anetumab ravtansine were consistent with earlier clinical findings. Detailed study results are expected to be presented at an upcoming medical meeting.
- Anetumab ravtansine is currently being investigated, as monotherapy and in combination, in additional studies, including a Phase Ib multi-indication study in six different types of advanced solid tumors, as well as a Phase Ib combination-study in patients with recurrent platinum-resistant ovarian cancer.
- • On November 9, 2015, a Phase 2 trial sponsored by Bayer was published on the NIH website ClinicalTrials.gov for anetumab ravtansine, also known as BAY 94-9343 and is currently recruiting participants.
Is
general: Yes
