Plitidepsin and lurbinectedin, two drugs advancing in clinical studies for the treatment of ovarian cancer and other malignancies, were the focus of two PharmaMar presentations at the April 1-5 American Association of Cancer Research (AACR) 2017 Annual Meeting in Washington, D.C.
The first presentation, “Plitidepsin targets the moonlighting functions of eEF1A2 in cancer,” revealed the exact mechanism of action of plitidepsin, a drug originally obtained from the sea squirt Aplidium albicans that binds to the eukaryotic elongation factor 1A2 (eEF1A2). The protein eEF1A2 has been found to be expressed in many tumors, including ovarian cancer and multiple myeloma.
Plitidepsin was assessed in the recently finished pivotal ADMYRE Phase 3 trial (NCT01102426) for the treatment of multiple myeloma. The study enrolled 255 U.S., European and Asian patients with relapsed and refractory multiple myeloma and who had received at least three but no more than six prior treatment regimens. Patients were randomized to receive either plitidepsin plus dexamethasone or dexamethasone alone.
The combo therapy reduced the risk of disease progression or death by 35 percent compared to dexamethsone alone. Based on the findings, Spain’s PharmaMar applied to the European Medicines Agency (EMA) in 2016 for marketing authorization, The request sought plitidepsin approval in combination with dexamethasone for patients with relapsed or refractory multiple myeloma. EMA has accepted the application for review and will likely make a decision in 2017.
The second presentation, “Lurbinectedin reverses platinum dependent IRF1 overexpression and nuclear localization, partially responsible for resistance to platinum drugs in ovarian cancer,” presented preclinical data of lurbinectedin, an investigational compound that has demonstrated a strong anti-proliferative activity against human tumor models.
Lurbenictedin acts as an inhibitor of the enzyme RNA polymerase II — an enzyme essential for protein production — causing cancer cell death, and halting tumor growth. In a prior Phase 2 trial, the drug induced an overall response rate of 22 percent and a disease control rate of 71 percent, showing activity in both platinum-resistant and platinum-refractory ovarian cancer patients. It proved that lurbinectedin is capable of reversing IRF-1-dependent resistance to Platinol (cisplatin) in ovarian cancer cells.
Lurbinectedin is also being studied in a Phase 2 trial of BRCA-mutated metastatic breast cancer (NCT01525589), where it induced an overall response rate of 41 percent, reaching the trial’s primary endpoint.It’s also the focus of two Phase 3 clinical trials in platinum-resistant ovarian cancer (NCT02421588) and in platinum-resistant small cell lung cancers (NCT02566993).
“To continue working so oncological patients can enjoy access to innovative treatments is a commitment PharmaMar acquired from the outset, one that lies behind every one of our decisions,” Luis Mora, managing director of PharmaMar’s oncology unit, said in a press release. “We hope that plitidepsin and lurbinectedin will become a reality in clinical oncological practice so that, together with Yondelis, they deliver new options to patients and specialists.”