Myriad Genetics has filed a supplementary premarket approval (sPMA) application with the U.S. Food and Drug Administration (FDA) seeking approval of its myChoice CDx test to identify advanced ovarian cancer patients more likely to benefit from treatment with Zejula (niraparib) after responding to first-line platinum-based chemotherapy.
MyChoice CDx is a test that determines DNA repair defects in tumors — or homologous recombination deficiency (HRD)-positive tumors — by assessing mutations in the BRCA1 and BRCA2 genes (involved in DNA repair), along with three biomarkers of genomic instability. Genomic instability refers to the high frequency of mutations within the genome.
Because tumors with such defects are more dependent on other DNA repair mechanisms involving the PARP enzyme — a DNA damage sensor — they are more likely to respond to treatments, like Zejula, that block PARP activity (PARP inhibitors).
Zejula — marketed by Tesaro, a subsidiary of GlaxoSmithKline (GSK) — is approved in the U.S. and Europe as a maintenance therapy for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are responding at least partly to platinum-based chemotherapy (usually cisplatin or carboplatin).
The FDA extended Zejula’s indication to include women with HRD-positive tumors who have received at least three prior lines of chemotherapy in October 2019. At the same time, it also approved myChoice CDx as a companion diagnostic test to identify advanced ovarian cancer patients who are eligible for Zejula late-line treatment.
With this new application, Myriad hopes to expand myChoice CDx’s use to include the identification of women who are more likely to benefit from Zejula maintenance treatment after responding (partly or completely) to first-line platinum-based chemotherapy.
“The myChoice CDx test provides valuable molecular insights into tumors and helps identify women with ovarian cancer who are most likely to benefit from PARP inhibitors,” Nicole Lambert, Myriad’s president, said in a press release.
“This regulatory submission represents another important step forward for precision medicine and ensuring that women have access to the most advanced therapies,” Lambert added.
The application is supported by positive data from the PRIMA Phase 3 trial (NCT02655016) showing that among women with advanced ovarian cancer who responded to first-line platinum-based chemotherapy, those with HRD-positive tumors (identified by myChoice CDx) benefited most from Zejula compared to a placebo.
PRIMA, conducted in 20 countries across 181 clinical sites, included 733 women with newly diagnosed advanced cancer of the ovary, peritoneum, or fallopian tube, who responded to first-line platinum-based chemotherapy and were at high risk for relapse.
About half of the women (51%) had HRD-positive tumors, based on myChoice CDx test results.
Participants were randomly assigned to either 300 mg of Zejula (487 women) or a placebo (246 women) daily, in 28-day cycles, within 12 weeks of completing the last chemotherapy cycle. Treatment was given for 36 months or until disease progression.
Results showed that women treated with Zejula lived significantly longer without signs of disease progression (progression-free survival, PFS) than did those on a placebo (median of 13.8 months vs. 8.2 months). This resulted in a 38% reduction in the risk of disease progression or death with Zejula’s use.
Notably, among those with HDR-positive tumors, an even greater reduction (by 57%) in the risk of disease progression or death was seen in Zejula-treated women — their median PFS was 21.9 months, compared with 10.4 months in these women on a placebo.
The 24-month overall survival of women with HDR-positive tumors also favored Zejula (91% of women) over placebo (85% of women), representing a 40% reduction in the risk of death at two years.
The trial’s results were presented at the European Society for Medical Oncology (ESMO) 2019 congress, held in Barcelona, and simultaneously published in the New England Journal of Medicine in September 2019.
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