Amgen Terminates Rilotumumab Clinical Studies In Advanced Gastric Cancer

Amgen has announced that it is terminating all Amgen-sponsored clinical studies of rilotumumab in advanced gastric cancer. The company published its decision in a press release, stating that terminated studies include the Phase 3 RILOMET-1 and RILOMET-2 studies. An independent data monitoring committee (DMC) reviewed the RILOMET-1 study and found increased deaths in the rilotumumab and chemotherapy group compared to the chemotherapy treatment only arm.

Sean E. Harper, M.D., EVP of Research and Development at Amgen, said, "While we are disappointed with these results, we will work with lead investigators to further analyze the data in order to help inform future research and therapies in this area.”

Rilotumumab Study Termination

Amgen stated it was terminating all studies it was conducting, indicating that other entities are conducting studies with rilotumumab. Currently, the National Cancer Institute (NCI), the Southwest Oncology Group, and the Gynecologic Oncology Group are conducting studies of rilotumumab. During a planned safety review, the Amgen’s DMC found an increasing number of deaths. Amgen states that it will communicate with investigators and provide guidance for study subjects. The company also intends to present and publish data from the trial. Rilotumumab, formerly AMG-102, is a monoclonal antibody that inhibits the hepatocyte growth factor/scatter factor (HGF/SF), MET pathway. Its action reduces cell growth and prevents tumor cell migration.

Study Termination Protocols

When a drug sponsor terminates a study or the Food and Drug Administration (FDA) stops a trial, the sponsor has certain responsibilities to the subjects who were taking the drug or biologic. In rilotumumab’s case, patients were dying at an alarming rate so study cessation was in the patients’ interest. However, studies are halted or stopped that may affect patients negatively.

The FDA has provided guidance on the DMC’s role in clinical trials, including termination of studies. The FDA states, “In almost all cases, a DMC is advisory to the sponsor; the sponsor decides whether to accept recommendations to discontinue a trial. FDA will rarely, if ever, tell a sponsor which decision to make.” Therefore, in Amgen’s rilotumumab study termination, it is likely that the statisticians in Amgen’s DMC informed the company of the irregularities, and Amgen made the decision to terminate without the FDA’s input.

The FDA does require though, that the drug sponsor inform the federal agency of trial cessation, preferably in advance. Properly notified, the FDA is enabled to support investigators, clinical sites, and patients in trial discontinuation.