Abstract RF7-01: Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study

Abstract Background: Disease progression in patients (pts) with ER+/HER2- mBC on 1L endocrine therapy (ET) + CDK4/6i is associated with mechanisms of resistance that impact the efficacy of subsequent therapy. Later treatment options include ET ± targeted agents (CDK4/6i or PI3K/AKT/mTOR pathway inhibitors). Clinical trials have shown mPFS of 3.6-6.8 mo with ET + everolimus(Cook 2021, Vasseur 2024) and mPFS of 5.3-9.4 mo by switching the CDK4/6i(Kalinsky 2023, 2024, Jhaveri 2024). Elacestrant (Ela) significantly improved PFS vs SOC ET (ESR1m tumors HR 0.55; 95% CI0.39-0.77; all pts HR 0.70; 95% CI 0.55-0.88) with manageable safety in the EMERALD trial (Bidard 2022). Based on encouraging clinical activity and tolerability from Ph 1b, we evaluated the Ph 2 combinations of Ela + everolimus(Eve) or abemaciclib (Abema) in all pts and clinically relevant subgroups. Methods: ELEVATE is evaluating elacestrant combined with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib,or palbociclib to address different resistance mechanisms. Patients with ER+/HER2- mBC and 1-2L of prior ET are eligible regardless of ESR1mstatus. Prior CDK4/6i is required for Arm B (Ela + Eve) and Arm C (Eve + Abema). Patients with no prior CDK4/6i were enrolled in Arm D (Ela + Abema). The Ph 2objective is to evaluate PFS with each combination. ESR1 and PIK3CA mutation status were evaluated in pts for both combinations Ela + Eve (n=48) and Ela + Abema(n=50). Results: As of September 2025,50 pts enrolled in Arm B (Ela + Eve), and 60 enrolled in Arms C and D (Ela + Abema combinations, n=30 each). Baseline characteristics include pts with visceral metastases (72% Arm B, 92% Arms C/D), primary ET resistance (20% Arm B, 15%Arms C/D), ESR1m (42% Arm B, 33% Arms C/D), and PIK3CAm (50% Arm B,27% Arms C/D). PFS benefit was consistent across subgroups, including those with visceral metastases, prior fulvestrant or primary ET resistance. The Ela combinations demonstrate safety consistent with the known safety profiles of Eve or Abema + SOC ET. Ph 2 Ela + Eve ORR was 19.5%,SD was 63.4%, DCR 82.9%, and mDOR 8.54 months. Ph 2 Ela + Abema ORR was 24.6%,SD was 66.7%, DCR 91.2%, and mDOR 14.75 months. mPFS results are summarized in Table 1. The median follow period for Ela + Abema is 8.6 (6.5-11.1) months. Updated efficacy results with longer follow-up will be provided for this combination. Conclusion: Elacestrant in combination shows a consistent PFS benefit irrespective of ESR1m status in pts with ER+/HER2-mBC after progressive disease on ET ± prior CDK4/6i. Elacestrant has the potential to become an ET backbone for combination strategies with targeted agents, supporting an all-oral approach that may delay the need for chemo or ADC-based regimens in this patient population. Citation Format: H. Rugo, S. M. Tolaney, N. Chan, G. Borges, R. Yerushalmi, M. Sharifi, W. McHayleh, T. Beck, N. Vidula, E. Hamilton, K. J. Rinn, J. O’Shaughnessy, G. Curigliano, J. Cortés, P. Romero, G. Tonini, A. Paoli, M. Binaschi, L. Cheng, J. Crozier, T. Wasserman, V. Kaklamani. Elacestrant in combination with everolimus or abemaciclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC): phase 2 results from ELEVATE, an open-label, umbrella study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF7-01.