The US FDA has granted full approval to Inluriyo (imlunestrant), an oral selective estrogen receptor degrader (SERD), in combination with Verzenio (abemaciclib), a CDK4/6 inhibitor, for adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–), ESR1-mutated locally advanced or metastatic breast cancer (MBC) whose disease has progressed on at least one prior line of endocrine therapy. The approval, granted to Eli Lilly and Company (NYSE: LLY), marks the second FDA authorization for imlunestrant in under a year, following its September 2025 monotherapy approval in the same indication.
The combination is indicated for patients whose tumors harbor an ESR1 mutation as detected by an FDA-authorized test, and is administered orally — imlunestrant at 400 mg once daily on an empty stomach and abemaciclib on its standard twice-daily schedule. The approval received full rather than accelerated status.
The approval is supported by data from the Phase III EMBER-3 trial (NCT04975308), a randomized, open-label study in patients with ER+, HER2– locally advanced or MBC who had progressed on an aromatase inhibitor (AI) with or without a CDK4/6 inhibitor. In the ESR1-mutated subgroup (n=159), imlunestrant plus abemaciclib doubled median progression-free survival (PFS) compared with imlunestrant alone: 11.1 months versus 5.5 months (hazard ratio 0.53; 95% CI, 0.35–0.80). The most common Grade 3/4 adverse events included decreased neutrophils (21%) and diarrhea (9%).
Imlunestrant binds to and degrades the estrogen receptor, maintaining activity against ESR1-mutant receptors that become constitutively active following AI exposure — a resistance mechanism occurring in approximately 50% of patients with ER+, HER2– MBC treated with prior endocrine therapy. Combining it with abemaciclib, which inhibits CDK4 and CDK6 to slow cell-cycle progression, targets two mechanistically distinct drivers of tumor growth simultaneously.