Abstract PS1-08-06: Results of the phase 2 SUMIT-BC study, a randomized controlled trial of the cyclin-dependent kinase 7 inhibitor (CDK7i) samuraciclib with fulvestrant in advanced hormone receptor positive (HR+) breast cancer after a CDK4/6 inhibitor (CDK4/6i)

Abstract Background: Samuraciclib (CT7001) is a small molecule, ATP competitive, selective oral inhibitor of the tumorigenic effects of CDK7. A phase I study in patients with HR+/HER2− advanced breast cancer (BC) who had previously been treated with a CDK4/6i demonstrated a favorable safety profile and clinical activity when combined with fulvestrant Coombes et al. Nature Comms 2023. This study showed that patients with no detectable TP53 mutation (TP53mt) in ctDNA at baseline and those without baseline liver metastases appeared to have better outcomes, a finding repeated in a second independent trial Oliveira et al. ESMO BC 2025. The phase 2 randomized SUMIT-BC (NCT05963984) study was designed to evaluate the efficacy, safety, pharmacokinetics (PK), and quality of Life (QoL) of samuraciclib combined with fulvestrant compared to fulvestrant monotherapy. Methods: Eligible patients were ≥18 years with histologically or cytologically confirmed ER+/HER2− locally advanced or metastatic BC not amenable to resection or radiotherapy of curative intent, had received an aromatase inhibitor (AI) combined with a CDK4/6i in the adjuvant or advanced setting, and had RECIST v1.1 evaluable disease. Baseline TP53 status was established using Guardant360 ctDNA analysis. Patients were randomized 1:1:1 to samuraciclib 360 mg QD + fulvestrant 500 mg IM, samuraciclib 240 mg QD + fulvestrant, or fulvestrant alone. Samuraciclib was administered as a new single oral tablet formulation. The primary endpoint was clinical benefit rate at 24 weeks. Secondary endpoints were tolerability, progression-free survival, overall response rate, duration of response, and PK of fulvestrant and samuraciclib. Results: 87 patients were screened and 59 were randomized to samuraciclib 360 mg + fulvestrant (n=20), samuraciclib 240 mg + fulvestrant (n=19), or fulvestrant alone (n=20). Data cut-off was September 2, 2025. Patient and disease characteristics and efficacy and safety results are shown in the table. No responses occurred in patients with detectable TP53mt. The most common AEs were gastrointestinal (GI). One patient treated with samuraciclib 240 mg discontinued due to GI AEs. Dose reduction permitted patients to stay on treatment long term. Samuraciclib single tablet exposure was consistent with that observed after dosing with the multiple capsules used in early development. Conclusions: Samuraciclib QD combined with fulvestrant demonstrated promising efficacy in ER+/HER2− locally advanced or metastatic BC previously treated using an AI with a CDK4/6i. The most common AEs were dose-related GI AEs. Pharmacokinetics of the new tablet formulation were acceptable. These data indicate that a phase 3 trial of samuraciclib with fulvestrant in a population with no TP53mt is warranted. Citation Format: S. Pernas, C. Karaçin, C. A. González-Núñez, S. Aksoy, M. Bellet Ezquerra, N. Karadurmuş, O. Yazıcı, M. Abu-Khalaf, B. Bermejo, M. González Cordero, M. Gümüş, C. Hinojo González, R. Lozano Mejorada, E. de la Mora Jiménez, C. Zuloaga Fernandez del Valle, Ç. Arslan, S. Kurian, M. Castro-Henriques, D. Motola Kuba, J. Pascual, T. Pluard, G. Szentmártoni, F. Moreno, G. Clack, S. McIntosh, R. Coombes. Results of the phase 2 SUMIT-BC study, a randomized controlled trial of the cyclin-dependent kinase 7 inhibitor (CDK7i) samuraciclib with fulvestrant in advanced hormone receptor positive (HR+) breast cancer after a CDK4/6 inhibitor (CDK4/6i) 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 PS1-08-06.