Elacestrant hydrochloride

The Swiss pharma arrived at the European Society for Medical Oncology conference in Berlin armed with detailed data from the phase 3 trial.\n Roche’s giredestrant was shown to reduce the risk of breast cancer progression or death by 62% for a specific cohort of a phase 3 trial, as the pharma plans for the oral selective estrogen receptor degrader (SERD) to benefit “all comers.”The evERA trial enrolled people with ER-positive, HER2-negative locally advanced or metastatic breast cancer who had previously received a CDK 4/6 inhibitor and endocrine therapy. Patients received the all-oral combination of giredestrant and Afinitor (everolimus) or standard of care.Roche announced last month that the study hit its co-primary endpoints of demonstrating better progression-free survival (PFS) than standard of care in both the intention-to-treat (ITT) and ESR1-mutated populations. The Swiss pharma arrived at the European Society for Medical Oncology (ESMO) conference in Berlin this weekend armed with detailed data.The findings tied giredestrant to 44% and 62% improvement in PFS for the ITT and ESR1 cohorts, respectively. Median PFS was 8.7 months in the ITT arm and 9.9 months in the ESR1-mutated population, compared to 5.4 months for the comparator arms.While the most impressive data was from the ESR1-mutated patients, the pharma is confident that giredestrant will “work in all-comers,” according to Charles Fuchs, M.D., global head of oncology and hematology drug development.“Our goal was—and still is—to make this drug available and useful for all-comers and across all settings of metastatic and curative settings of HR-positive breast cancer,” Fuchs told Fierce in an interview on the sidelines of the conference.“When we look at overall survival, which is immature for the non-mutants, we see a hazard ratio and a trend that we think is clinically meaningful,” he added. It means Fuchs and his team remain confident that giredestrant can take on the competition, such as AstraZeneca’s injectable SERD Faslodex, also known as fulvestrant.“We think, in aggregate, the totality of the evidence says that giredestrant is better than fulvestrant, not only in the intent-to-treat and the mutants, but in the non-mutants,” he added. “And we believe this drug should be available in this setting, in this combination, for all patients.”As part of this strategy, Roche is already evaluating giredestrant in four other late-stage breast cancer studies, including the persevERA trial for estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer, which is due to read out in the first half of next year.Roche “feels good about” persevERA, according to Fuchs, who cited previous clinical evidence showing that “in a setting where the tumor is sensitive to ER, it does appear to be better.”The data update at ESMO marks an ongoing return to favor for giredestrant after the drug contributed to a downturn in excitement about oral SERDs in 2022. That year, giredestrant failed a midphase breast cancer test, while Sanofi’s rival asset amcenestrant flunked a pivotal trial. The field has shifted again since then, with Menarini’s Orserdu coming to market in second-line patients and AstraZeneca’s camizestrant improving outcomes in first-line patients with emergent ESR1 mutations.Looking back at that bump in the road for giredestrant, Fuchs described the failed breast cancer study as “really a high-risk bet in a population that was extremely endocrine-resistant.”“So I think it was a useful phase 2 study,” he concluded. “We learned a lot from it … and we now have studies that I think are designed to test the right hypothesis.”

Roche’s breast cancer pill giredestrant is the first member of its class — the selective estrogen receptor degraders, or SERDs — to prove itself effective in patients who do not have a mutated version of the receptor that these drugs target. The findings, which are set to be presented Saturday at the European Society for Medical Oncology’s annual meeting in Berlin, could give Roche’s pill an advantage against the SERD pills on the market, including Eli Lilly’s newly approved Inluriyo and Menarini’s Orserdu. Those drugs have only been shown to work in patients with mutations in the gene for the ESR1 receptor, which SERDs are designed to inactivate. In non-mutated patients, giredestrant yielded a 16% decrease in the risk of death or disease progression versus standard of care, Roche’s head of oncology and hematology product development Charlie Fuchs told Endpoints News before the presentation. The data came from the Phase 3 evERA trial . In mutated patients, the risk of disease progression or death was cut by 62% versus control. And in the overall trial population, which is also called the intent-to-treat population, the risk was reduced by 44%, which Fuchs describes as “pretty meaningful.” Around 55% of the patients in the trial had ESR1 mutations, he said. Roche intends to seek approval for the drug, but Fuchs declined to provide specifics about timing. In the overall population, median progression-free survival was 8.8 months in the giredestrant arm compared with 5.5 months with standard care. The difference was statistically significant, with a p-value of less than 0.0001. In the ESR1-mutated population, median PFS was 9.99 months versus 5.5 months with control — that’s also good for significance, with a similar p-value. “To our knowledge, [no one has] shown what we think is a clinically meaningful and significant benefit in the intent-to-treat population,” Fuchs said. “In terms of a compelling body of evidence supporting both mutants and intent-to-treat, I think this study is unique.” The trial continues, with the aim of also proving a benefit in overall survival. The data presented at ESMO showed that the drug reduced the risk of death by 31% and 38% in the overall and mutant populations versus control, but neither arm has hit significance yet. “Overall survival is still very immature,” Fuchs said, “but we’re seeing a really encouraging, positive trend in overall survival, both in the mutants and the non-mutants.” Fuchs said the non-mutant patients given giredestrant also saw improvements in secondary endpoints, including objective response rate and duration of response. The objective response rate was 20.0% in non-mutant patients given the SERD, versus 8.7% for non-mutant patients in the control arm. The company believes this drives clinical benefit, he said. Median duration of response was also longer, at 12.7 months for giredestrant recipients and 7.7 months for those who received standard of care. “We think the benefit of giredestrant is driven by both populations — somewhat differentially, as might be expected — but both, we think, are clinically meaningful,” Fuchs said. Roche described the SERD’s side effects as “manageable,” with no new safety signals or ocular toxicity. Patients in the evERA trial took giredestrant in combination with a generic antiproliferative, with the control arm patients taking everolimus plus endocrine therapy. The patients had estrogen receptor-positive, HER2-negative, locally advanced or metastatic breast cancer, and had been treated with CDK4/6 inhibitors and hormone therapy. Treatment with CDK4/6 inhibitors can induce ESR1 mutations. How much of an advantage giredestrant might have over its competitors remains to be seen. But Fuchs is confident. “We think the drug is differentiated compared to the other drugs in development,” he said. “What we can say is it’s the most potent SERD currently.”