Abstract CT262: Elacestrant (Ela) in combination with everolimus (Eve) or abemaciclib (Abema) 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 pts with ER+/HER2- mBC on 1L ET + CDK4/6i is associated with mechanisms of resistance that impact the efficacy of subsequent therapy. Ela improved PFS vs SOC ET (ESR1m tumors HR 0. 55; 95% CI 0. 39-0. 77; all pts HR 0. 70; 95% CI 0. 55-0. 88) with manageable safety in the Ph3 EMERALD trial (Bidard 2022). ELEVATE is evaluating Ela combined with Eve, alpelisib, capivasertib, Abema, ribociclib, or palbociclib to address resistance mechanisms. Based on encouraging Ph1b results, we evaluated Ph2 combinations of Ela + Eve or Abema in all pts and subgroups. Methods: Pts with ER+/HER2- mBC, 1-2L of prior ET are eligible regardless of ESR1m status. Prior CDK4/6i is required for Arm B (Ela + Eve) and Arm C (Eve + Abema). Pts with no prior CDK4/6i were enrolled in Arm D (Ela + Abema). Ph2 evaluates 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 Sept 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 are pts with visceral mets (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 was consistent across subgroups (Table 1). Safety results were consistent with the known profiles of Eve or Abema + SOC ET. Ph2 Ela + Eve ORR was 19. 5%, DCR 82. 9%, mDOR 8. 54 mo. Ph2 Ela + Abema ORR was 24. 6%, DCR 91. 2%, mDOR 14. 75 mo. Conclusion: Ela combinations show a consistent clinically meaningful PFS irrespective of ESR1m status in pts with ER+/HER2- mBC after progressive disease on ET ± prior CDK4/6i, and could become an ET backbone for combination strategies, supporting an all-oral approach. Citation Format: Hope S. Rugo, Sara M. Tolaney, Nancy Chan, Giuliano Borges, Rinat Yerushalmi, Marina N. Sharifi, Wassim McHayleh, Thaddeus Beck, Neelima Vidula, Erika Hamilton, Kristine J. Rinn, Joyce O’Shaughnessy, Giuseppe Curigliano, Javier Cortés, Paula Muñoz Romero, Giulia Tonini, Alessandro Paoli, Monica Binaschi, Li Cheng, Jennifer A. Crozier, Tomer Wasserman, Virginia Kaklamani. Elacestrant (Ela) in combination with everolimus (Eve) or abemaciclib (Abema) 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 American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT262.