Phase Ib randomized open-label trial of sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus nivolumab and relatlimab as second-line therapy metastatic triple negative breast cancer: SIMONE trial.

Abstract

TPS1164 Background: The use of immunotherapy beyond first-line setting is not yet routine in the treatment arsenal of patients with metastatic triple-negative breast cancer (TNBC), and this opens an opportunity for clinical trials examining whether adding novel immunotherapy agents to standard of care therapies would benefit patients. Prior studies have combined immunotherapy with standard chemotherapy (Cortes J, NEJM 2022), but combining immunotherapies with antibody-drug conjugates (ADCs) is a strategy worth pursuing given improvement of outcomes of ADCs when compared to standard chemotherapy (Bardia A et al, NEJM 2021). Sacituzumab govitecan (SG), a TROP2-ADC, is currently the standard second-line therapy for patients with metastatic TNBC, and in this study it is being combined with either nivolumab (programmed cell death [PD-1] inhibitor) or nivolumab plus relatlimab (lymphocyte activation gene-3 [LAG3]-inhibitor) due to preliminary data showing that simultaneous PD-1 and LAG3 inhibition enhances the anti-tumor immune response and restores the effector function of exhausted T-cells (Woo S-R et al, Cancer Res 2012; Tawbi HA et al, NEJM 2022). Methods: This is an ongoing investigator-initiated randomized, open-label, phase Ib study to assess safety and efficacy of SG plus nivolumab (n= 30 patients) or SG plus a fixed dose combination (FDC) of nivolumab and relatlimab (n = 30 patients) in patients with metastatic TNBC; NCT06963905. The study is accruing patients whose tumors are PD-L1 positive (combined positive score >10) and an amendment in under review to also include patients whose tumors are PD-L1 negative on routine testing, with 1 prior line of cytotoxic chemotherapy with or without prior immunotherapy use in the metastatic setting or within 6 months from completion of curative intent treatment. Study treatment will be continued until progression of disease, unacceptable toxicity, death, or withdrawal of consent. Safety will be monitored, and tumor response will be regularly evaluated by RECIST 1.1 criteria every 9 weeks. The primary endpoint includes safety as the incidence of dose-limiting toxicities (DLT) in 3 weeks after C1D1. Secondary endpoints include objective response rate (defined as either complete response or partial response), duration of response, clinical benefit rate (objective response plus stable disease), progression-free survival, and safety with SG plus nivolumab or SG plus nivolumab + relatlimab FDC. Exploratory endpoints include overall survival, and biomarkers of prediction of response and resistance. There will be a follow-up visit after the last study treatment administration or before starting a new anticancer treatment, whichever occurs first, followed by long-term/survival chart review follow-up every three months for 2 years. Clinical trial information: NCT06963905 .