Abstract OT2-27-01: Solti-1718 NEREA Trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-enriched (HER2-E) advanced breast cancer (BC)
Authors: Ciruelos Eva , Saura Cristina , González-Farré Xavier , Bofill Javier Salvador , Vidal Maria , Blancas Isabel , López-Miranda Elena , Iglesias Maria , Arumi Miriam , Margelí Mireia , Pulido Catarina , Morales Serafin , Henao Fernando , Sánchez Pilar , Alves Sara , Branco Diogo , Gasent Joan Manel , Sánchez-Rovira Pedro , Godoy Ana , Passos-Coelho José L. , Escrivá-de-Romaní Santiago , Ferrero-Cafiero Juan M , Pascual Tomás , Prat Aleix 
Published: March 2022

Background HR+/HER2-negative BC represents ∼70% of all newly diagnosed breast tumors. BC is a clinically and biologically heterogeneous disease where intrinsic subtypes play a role. Non-luminal subtypes within HR+/HER2-negative disease do not benefit to the same extent from the standard of care treatments as the luminal subtypes. Thus, other strategies are needed. HER2-E subtype represents approximately 6.6-11.0% of HR+/HER2-negative tumors and is enriched in twice as many cases in metastatic tumors. According to EGF30008 trial, HER2-E advanced BC patients despite presenting poor outcomes across treatments showed benefit from anti-HER2 therapy. SOLTI-1718 NEREA aims to evaluate whether EGFR/ERBB2 axis inhibition by neratinib improves efficacy in terms of progression-free survival (PFS) in patients with advanced HR+/HER2-negative disease resistant to endocrine treatment (ET). Methods SOLTI-1718 NEREA (NCT04460430) is an open-label, single-arm, multicenter, and multinational phase II clinical trial following a Simon’s 2-stage design with one interim and one final efficacy analysis. Locally advanced or metastatic HER2-E (determined at metastatic sample), HR+/HER2-negative BC patients who had recurrence or progression while receiving previous ET (with or without a CDK4/6 inhibitor) will be included. ≤ 1 prior line of chemotherapy will be allowed. The primary objective is to assess the efficacy of neratinib in combination with ET in HER2-E, HR+/HER2-negative patients in terms of PFS6 by local assessment by the investigator using RECIST v.1.1. Secondary endpoints include clinical benefit rate at 6 months, overall response rate, duration of response, time to response and incidence, duration, and severity of adverse events. The treatment schedule will consist of neratinib 240 mg daily in combination with ET, with either exemestane, fulvestrant, or tamoxifen (as per the investigator´s decision). All patients will take prophylactic loperamide with an established dosing scheme during the first cycle and on-demand in subsequent cycles. Tumor assessments will be performed at baseline and every 8 weeks during the first year, and every 12 weeks thereafter. An interim analysis will be performed after 33 patients are evaluable. If 15 to 27 patients achieve a PFS at 6 months (PFS6), the trial will continue to the second stage, otherwise, it will be stopped for futility (&lt;15) or efficacy (≥28). A total of 56 evaluable patients will be included in stages I and II. The Spanish regulatory national competent authority approved the study on April 8th 2020. Recruitment started in July 2020. As of June 2021. Seven patients have been enrolled in 15 sites in Spain and 3 sites in Portugal. Acknowledgments: We thank PUMA BIOTECHNOLOGY, INC for their provision of Neratinib and financial contribution to the study.

Citation Format: Eva Ciruelos, Cristina Saura, Xavier González-Farré, Javier Salvador Bofill, Maria Vidal, Isabel Blancas, Elena López-Miranda, Maria Iglesias, Miriam Arumi, Mireia Margelí, Catarina Pulido, Serafin Morales, Fernando Henao, Pilar Sánchez, Sara Alves, Diogo Branco, Joan Manel Gasent, Pedro Sánchez-Rovira, Ana Godoy, José L. Passos-Coelho, Santiago Escrivá-de-Romaní, Juan M Ferrero-Cafiero, Tomás Pascual, Aleix Prat. Solti-1718 NEREA Trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-enriched (HER2-E) advanced breast cancer (BC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-27-01.