SEGNO: An exploratory study of the safety and efficacy of genomic biomarker-guided neoadjuvant therapy for locally advanced and oligometastatic prostate cancer

BackgroundNeoadjuvant therapy (NT) was reported to be associated with improved pathological outcomes, but was of limited value in improving the survival outcomes for patients with locally advanced prostate cancer (PC), which may be attribute to the heterogeneous nature of PC. Additionally, several clinical trials demonstrated that NT followed by radical prostatectomy (RP) may improve the oncological outcomes of oligometastatic prostate cancer (OMPC). With the advancement of molecular sequencing techniques and targeted agents approved for special populations, genomic biomarker-guided NT for PC has been rapidly evolving and assumed to improve the prognosis outcomes.Trial designThe ongoing SEGNO trial is an open-label, multi-arm, Phase 2 study assessing the safety, efficacy of genomic biomarker-guided NT for locally advanced PC and OMPC (defined as no visceral metastasis and ≤5 bone metastases). According to the results of the genomic profile, participants (N = 40) will be assigned to 4 NT groups: Arm 1: Homologous recombination repair (HRR) alterations (BRCA1/2) (Rezvilutamide: 240 mg PO QD + goserelin microspheres: 3.6 mg IM Q4W + parmiparib: 60 mg PO QD); Arm 2: HRR alterations (except BRCA1/2 and CDK12) (Rezvilutamide: 240 mg PO QD + goserelin microspheres: 3.6 mg IM Q4W + cisplatin: 70 mg/m2 IV Q3W); Arm 3: MSI-H/dMMR, TMB≥10 mut/Mb or CDK12 alterations without other HRR alterations (Rezvilutamide: 240 mg PO QD + goserelin microspheres: 3.6 mg IM Q4W + tislelizumab: 200 mg IV Q3W); Arm 4: No targetable actionable aberration (Rezvilutamide: 240 mg PO QD + goserelin microspheres: 3.6 mg IM Q4W + docetaxel: 70 mg/m2 IV Q3W). A following prostate-specific membrane antigen positron emission tomography/ computed tomography and RP plus pelvic lymph node dissection will be performed after 6 cycles of NT. The primary endpoints are rates of clinical complete response, pathological minimal residual disease (defined as residual tumor 5 mm or less) and complete pathologic response. Secondary endpoints include overall survival, progression-free survival and safety outcomes.Clinical trial identificationNCT06387056.Legal entity responsible for the studyThe First Affiliated Hospital of Xiamen University.Funding BeiGene (Beijing) Co., Ltd. and Jiangsu Hengrui Pharmaceuticals Co., Ltd.DisclosureAll authors have declared no conflicts of interest.