Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial (NCT04975308) in patients with ER+, HER2- ABC and disease progression on/after aromatase inhibitor showed significant progression-free survival (PFS) improvement with imlunestrant (400mg once daily) over standard therapy (SOC: fulvestrant or exemestane) among patients with ESR1-mutations (ESR1m) as well as with imlunestrant (400mg once daily) + abemaciclib (150mg BID) over imlunestrant in all patients regardless of ESR1m. Here we present efficacy and safety analyses in the EA population.
The EA population included all patients from Japan, Korea, Taiwan, and China. Analysis methods were consistent with the primary report, though the study was not powered for confirmatory testing.
The EA population comprised 233 (27%) of the 874 intent‐to‐treat population in EMBER-3 (imlunestrant: 83; SOC: 84; imlunestrant+abemaciclib: 66); 51% received prior CDK4/6 inhibitor. Among 73 patients with ESR1m (imlunestrant: 30[36%]; SOC: 26[31%]), imlunestrant improved PFS vs SOC (HR=0.53 [95%CI:0.27-1.01]; median PFS 5.6vs3.8months). Imlunestrant did not improve PFS in the overall EA population (n=167; HR=1.05 [95%CI:0.73-1.51]). Imlunestrant+abemaciclib improved PFS vs. imlunestrant in all EA patients (n=133; HR=0.52 [95%CI:0.33-0.82]; median PFS 11.4vs5.5months), with benefit observed regardless of ESR1m status. Secondary analyses (PFS by BICR and ORR) in the EA population were consistent with primary analyses. Overall survival data were immature. Safety was consistent with the primary analysis (any TEAE: any-grade:88%vs76%vs100% imlunestrant vs SOC vs imlunestrant+abemaciclib, grade≥3:15%vs19%vs54%) (patients with ≥1 SAE: any-grade:11%vs11%vs17%, grade≥3:9%vs10%vs14%) (dose reductions due to AE: any-grade:2%vs0%vs52%, grade≥3:0%vs0%vs0%) (dose discontinuations due to AE: any-grade:2%vs0%vs11%, grade≥3:0%vs0%vs0%) (diarrhea was the most frequent adverse event; any-grade:20%vs10%vs85%, grade≥3:0%vs0%vs6%). Exposures and pharmacokinetics were similar in EA and non-EA populations.
Consistent with primary EMBER-3 analysis, this EA subpopulation analysis showed PFS benefit with imlunestrant vs SOC in patients with ESR1m and with imlunestrant+abemaciclib vs imlunestrant in all patients, regardless of ESR1m status, along with generally tolerable safety profiles.