Clovis Oncology’s PARP Inhibitor Rubraca Gets Greenlight from FDA in Prostate Cancer

Rubraca approved 

Clovis Oncology won a new approval for its PARP inhibitor, Rubraca (rucaparib), as a treatment for a specific type of prostate cancer. With the new approval, Rubraca becomes the first PARP inhibitor approved in a prostate cancer setting.

The U.S. Food and Drug Administration approved Clovis’ Rubraca for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. The FDA gave the green light for this indication under accelerated approval based on objective response rate (ORR) and duration of response (DOR) data from the Phase II TRITON2 clinical study. The TRITON3 clinical trial is expected to serve as the confirmatory study for the Rubraca accelerated approval in mCRPC, Clovis said in its announcement.

In the TRITON2 study, patients treated with Rubraca saw a 44% objective response rate. The median DOR was not evaluable at the time of the data cut-off, Clovis said.  Additionally, a 55% confirmed prostate-specific antigen response rate was observed in an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or non-measurable disease, the company added.

Wassim Abida, an oncologist with Memorial Sloan Kettering and principal investigator for the TRITON2 study, said standard treatment options for mCRPC have been limited to androgen receptor-targeting therapies, taxane chemotherapy, Radium-223 and sipuleucel-T. Rubraca, he added, it’s the first in a class of drugs for patients with mCRPC who have a deleterious BRCA mutation.

“Given the level and duration of responses observed with Rubraca in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population,” Abida said in a statement.

PARP stands for poly ADP ribose polymerase, which is an enzyme many cancer cells are more dependent upon than regular, healthy cells are. PARP inhibitors are designed to disable DNA repair pathways in cancer cells, which make it difficult for those cells to survive.

Howard Soule, chief science officer of the Prostate Cancer Foundation noted that there have been several new drugs made available for prostate cancer over the past few years, but said “most men living with advanced stages of this disease continue to face a difficult journey with few treatment options.”

According to the American Cancer Society, approximately 192,000 men will be diagnosed with prostate cancer in 2020. Metastatic castration-resistant prostate cancer, or mCRPC, is an incurable disease, usually associated with poor prognosis. Approximately 43,000 men in the U.S. are expected to be diagnosed with mCRPC in 2020. About 12% of patients with mCRPC harbor a deleterious germline and/or somatic mutation in the genes BRCA1 and BRCA2.  The five-year survival rate for mCRPC is approximately 30%, Clovis said. 

This is the third approval for Clovis’ Rubraca, an inhibitor of PARP1, PARP2 and PARP3. The drug has also been approved as a treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer.