FDA Grants Breakthrough Therapy Designation to Rucaparib in Advanced Ovarian Cancer With BRCA Mutations


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The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Clovis Oncology’s investigational agent rucaparib as monotherapy treatment of advanced ovarian cancer in patients who have received at least two lines of prior platinum-containing therapy, with ­BRCA-mutated tumors, inclusive of both germline BRCA and somatic BRCA mutations.

Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 being developed for the treatment of platinum-sensitive ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, commonly referred to as “BRCA-like” or “BRCAness.” The Breakthrough Therapy designation was granted based on interim efficacy and safety results from two ongoing phase II studies of rucaparib in ovarian cancer, including a phase II study in women with germline BRCA mutations, and the ARIEL2 treatment study.

Clinical Data

A clinical data update from the ARIEL2 study presented at the 2015 Annual Meeting on Women’s Cancer demonstrated that 70% of evaluable patients with BRCA-mutant tumors achieved a RECIST and/or CA-125 response, and 65% achieved a RECIST response. Responses were observed in both germline and somatic BRCA-mutant tumors.

In addition, Clovis’ proprietary BRCA-like DNA signature, run by its partner Foundation Medicine, successfully predicted which ovarian cancer patients would respond to rucaparib therapy. In patients with normal BRCA genes, rucaparib activity was substantially higher for those with the prospectively defined BRCA-like homologous recombination deficiency (HRD) signature vs biomarker-negative patients. Forty-eight percent of patients with the BRCA-like signature achieved a RECIST and/or CA-125 response, and 40% achieved a ­RECIST response. In biomarker-negative patients, 8% of patients achieved a ­RECIST and/or CA-125 response.

These data also demonstrate that rucaparib is well tolerated. At the recommended phase II dose, the most common treatment-related adverse events reported in ≥ 15% of all patients included nausea, fatigue, transient alanine transaminase/aspartate transaminase elevations, dysgeusia, constipation, anemia/low hemoglobin, decreased appetite, vomiting, and diarrhea. These events were mostly grade 1/2; the only common grade 3/4 toxicity was anemia/low hemoglobin.

The next update of rucaparib clinical data will be presented at the 2015 ASCO Annual Meeting. ■



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