Everolimus

Eli Lilly has also been testing imlunestrant with the company's Verzenio in a broader breast cancer population. Eli Lilly has won the second FDA approval for an oral selective estrogen receptor degrader (SERD).Like the first oral SERD, Lilly’s imlunestrant is only cleared to treat ER-positive, HER2-negative advanced breast cancer that carries ESR1 gene mutations. Patients need to have tried at least one line of endocrine therapy to be eligible for imlunestrant, which will be sold under the brand name Inluriyo.“This represents an important advancement for patients with ESR1-mutated [metastatic breast cancer], a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance,” Komal Jhaveri, M.D., section head of endocrine therapy research and clinical director of early drug development at Memorial Sloan Kettering Cancer Center, said in a Sept. 25 release.Jhaveri is a principal investigator of the phase 3 Ember-3 trial, which supported Inluriyo’s approval. In the study, Inluriyo significantly reduced the risk of progression or death by 38% versus standard endocrine therapy in patients with ESR1-mutated ER-positive, HER2-negative breast cancer following progression on an aromatase inhibitor.While the study also recruited patients without ESR1 mutations, it failed to meet the progression-free survival efficacy bar in all patients.Before Lilly, Italian drugmaker Menarini had secured the first FDA approval for an oral SERD, also in ESR1-mutated breast cancer. Development of oral SERDs has quickly taken off as drugmakers hope to build on the success of AstraZeneca’s injectable SERD Faslodex.AZ recently reported a positive phase 3 for its oral SERD candidate camizestrant. The company’s Serena-6 trial adopts a novel design that incorporates camizestrant midway of first-line treatment after ESR1 mutation is detected and before disease progression.The British pharma has listed a regulatory decision based on Serena-6 as a first-half 2026 event in its second-quarter report in July. The company has a separate phase 3 trial, Serena-4, in a more traditional first-line setting that combines camizestrant with Pfizer’s CDK4/6 inhibitor Ibrance, with a readout expected in the second half of 2026.Lilly’s Inluriyo already has CDK4/6 combo data. In the same Ember-3 trial, a combination of Inluriyo and Lilly’s Verzenio led to a 43% reduction in the risk of death versus Inluriyo alone among patients with or without ESR1 mutations. In a subgroup of patients without the biomarker, the combo’s disease progression benefit was still strong at 41%.Because the combo arm was added to Ember-3 a few months after the study’s launch, data in this group were arguably less mature. At 15% data maturity, results on overall survival favored Inluriyo monotherapy over the Verzenio-Inluriyo combo in all patients regardless of ESR1 status.Lilly only filed Inluriyo as a monotherapy, a company spokesperson confirmed to Fierce Pharma. “Because the combination arm of the study began later than the monotherapy arm, those results are still maturing,” the spokesperson said. “Lilly has completed an updated analysis, which will be shared with the FDA and presented at a medical meeting later this year.” Meanwhile, Roche on Monday revealed that its oral SERD candidate giredestrant, used in combination with everolimus, improved progression-free survival in ER-positive, HER2-negative breast cancer patients who had tried a CDK4/6 inhibitor and endocrine therapy. The phase 3 evERA trial met both its co-primary endpoints as the combo showed “statistically significant and clinically meaningful” disease progression benefits in both the ESR1-mutated subgroup and the overall trial population, according to Roche. However, it remains to be seen whether the showing in all comers was driven by the ESR1 group.

Eli Lilly's oral selective oestrogen receptor degrader (SERD) Inluriyo (imlunestrant) was greenlit by the FDA on Thursday for certain patients with breast cancer, beating several other SERD developers to the punch. The drug will be available in the US "in the coming weeks," according to the pharma.Inluriyo can be used to treat adults with ER-positive, HER2-negative, ESR1-mutated, second-line advanced or metastatic breast cancer. The agency also cleared Guardant Health's Guardant360 CDx assay as a companion diagnostic to identify breast cancer patients with ESR1 mutations.The approval was based on data from the Phase III EMBER-3 trial, which were reported at the San Antonio Breast Cancer Symposium (SABCS) last December. Results from the study showed that Inluriyo reduced the risk of progression or death by 38% over standard endocrine therapy in ESR1-mutant patients, with median progression-free survival (PFS) of 5.5 months versus 3.8 months for the comparator.Investors were more excited, however, by findings in a separate EMBER-3 cohort that gave patients Inluriyo in combination with Lilly's CDK4/6 inhibitor Verzenio (abemaciclib). The duo achieved a median PFS of 9.4 months, reducing the risk of progression or death by 43% compared to the SERD alone — and the benefit was seen regardless of ESR1 or PI3K pathway mutation status, including in patients who had previously received CDK4/6 inhibitors (see – KOL Views Q&A: Battle for oral SERD supremacy in HR+ breast cancer boils down to efficacy). A spokesperson for Lilly told FirstWord that the combination arm of the study began later than the monotherapy arm, and its results are still maturing. The pharma has completed an updated analysis, which will be shared with the FDA and presented at a medical meeting later this year.Still, results from a recent FirstWord poll of 100 US and European oncologists suggest doctors are still eager to prescribe Inluriyo monotherapy. Nearly 75% of respondents said they are 'very' or 'extremely' likely to prescribe Lilly's oral SERD to ESR1-mutated patients in the second-line setting (see – Physician Views In-Depth: Oral SERDs on track to transform 2L care of ER+/HER2- breast cancer).Inluriyo is also being evaluated as an adjuvant treatment in the 8000-patient Phase III EMBER-4 trial in patients with ER-positive, HER2-negative early breast cancer at increased risk of recurrence.The SERD spaceThe monotherapy approval is a key regulatory win for Lilly, but several other drugmakers are racing toward the SERD finish line. At this year's American Society of Clinical Oncology (ASCO) meeting, Lilly further fleshed out its use case for Inluriyo with safety results and patient-reported outcomes from EMBER-3, while AstraZeneca presented data on its rival SERD, camizestrant, in the Phase III SERENA-6 study.While AstraZeneca reported a superior PFS of 16 months, the company used serial biopsies to  painstakingly predict ESR1 mutations and initiate therapy with camizestrant earlier in soon-to-be progressing patients who were already on a CDK4/6 inhibitor. The pinpoint precision contrasts with the broad activity seen with Lilly's Inluriyo-plus-Verzenio all-comers strategy Eli Lilly said it sees broad activity in an all-comers population in ER-positive/HER-negative breast cancer, while AstraZeneca used serial liquid biopsies to painstakingly predict ESR1 mutations and initiate therapy earlier in soon-to-be progressing patients.Jacob Van Naarden, EVP and President of Lilly Oncology, told FirstWord at the time that the patient burden of serial blood testing — financial, logistical and mental — sets a high bar for efficacy. For more from that interview, see Spotlight On: Pushback on AstraZeneca's new oral SERD strategy that 'doesn't really make a lot of sense'.Another oral SERD candidate is Roche's giredestrant, which recently impressed in the Phase III evERA study when given in combination with everolimus. The duo showed significant and clinically meaningful improvements on PFS in both patients with ESR1 mutations and the intention-to-treat population compared with endocrine therapy plus everolimus.And while Pfizer and Arvinas' oral PROTAC oestrogen receptor degrader vepdegestrant is under review at the FDA, the partners last week decided to step back from the programme and search for a third party to handle its commercialisation.