Roche's Giredestrant Combination Fails Phase III Trial in First-Line Breast Cancer
Roche's experimental breast cancer pill giredestrant combined with a CDK4/6 inhibitor failed to meet its primary endpoint in a Phase III trial for first-line treatment of ER-positive, HER2-negative advanced breast cancer, marking a setback for the drugmaker's next-generation hormone therapy program.
Roche on Monday said a Phase III trial of its selective estrogen receptor degrader (SERD) giredestrant in combination with a CDK4/6 inhibitor failed to meet its primary endpoint for the treatment of estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer. Patients treated with giredestrant and an older drug developed by Pfizer were no more likely to live without their cancer worsening than those given standard therapy.
The result is a setback because giredestrant is Roche's most advanced next-generation hormone therapy, part of a new class known as selective estrogen receptor degraders. The shares plunged following the announcement.
Despite this failure, the FDA has accepted a New Drug Application for giredestrant in a different setting. The filing acceptance is based on the Phase III evERA Breast Cancer study results, which showed that giredestrant plus everolimus reduced the risk of disease progression or death in people with ESR1-mutated, ER-positive advanced breast cancer who have had previous treatment with cyclin-dependent kinase (CDK)4/6 inhibitor and endocrine therapy. The FDA has set a Prescription Drug User Fee Act date of December 18.
Overall survival data were immature at the time of analysis, but a clear positive trend has been observed in the intention-to-treat population. Data from evERA are being used to support filing submissions to other global health authorities.
ER-positive breast cancer accounts for approximately 70% of all breast cancers. The evERA trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of patients develop ESR1 mutations.
evERA was the first positive Phase III readout for giredestrant, followed by lidERA Breast Cancer in the early-stage setting. The scientific rationale for lidERA was supported by prior results in the neoadjuvant setting, including the coopERA trial showing that giredestrant was superior to an aromatase inhibitor in reducing malignant cell division (Ki67 levels). In the coming weeks, Genentech will submit the giredestrant Phase III lidERA data in early-stage breast cancer to the FDA. The persevERA readout in first-line ER-positive breast cancer is expected in the first half of this year.
Giredestrant is an investigational, oral, potent next-generation selective estrogen receptor degrader and full antagonist. Giredestrant is designed to block estrogen from binding to the estrogen receptor, triggering its breakdown and stopping or slowing down the growth of cancer cells. Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy.