TPS4263 Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a 5-year survival rate of < 5%. Approved treatment options are limited to combination cytotoxic chemotherapy such as mFOLFIRINOX or nab-paclitaxel + gemcitabine. Cortisol-mediated glucocorticoid receptor (GR) activation provides prosurvival signals to tumor cells that contribute to chemotherapy resistance. The addition of relacorilant, a selective GR antagonist, to paclitaxel + gemcitabine improved tumor growth inhibition over paclitaxel + gemcitabine alone in a PDAC xenograft model (Greenstein Oncotarget 2021). Moreover, in a phase 1 study of relacorilant and nab-paclitaxel, 2 durable confirmed partial responses were observed in patients with mPDAC (Munster Clin Cancer Res 2022). The combination of relacorilant and nab-paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) in patients with platinum-resistant ovarian cancer in 2 randomized controlled trials, including the phase 3 ROSELLA study (Olawaiye Lancet 2025). The combination was well tolerated, with a safety profile that was consistent with nab-paclitaxel monotherapy. Therefore, the combination of relacorilant, nab-paclitaxel, and gemcitabine is deserving of further clinical study to improve outcomes in patients with mPDAC. Methods: TRIDENT is a phase 2, single-arm, open-label, multicenter study (NCT07259317) designed to evaluate the combination relacorilant + nab-paclitaxel + gemcitabine as a first-line treatment in mPDAC (target enrollment, N = 60). Key inclusion criteria are confirmed measurable metastatic disease (per Response Evaluation Criteria in Solid Tumors RECIST version 1.1), no prior systemic anticancer therapy to treat metastatic disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients will receive relacorilant 150 mg orally once daily for 3 consecutive days (day before, day of, and day after chemotherapy) in combination with nab-paclitaxel (100 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) given on days 1, 8, and 15 of each 28-day cycle. Treatment will continue until disease progression or unmanageable toxicity. The primary endpoint is investigator-assessed PFS per RECIST version 1.1 and will be analyzed using Kaplan-Meier methods. Secondary endpoints are OS, best overall response, objective response rate, clinical benefit rate at 24 weeks, duration of response, cancer antigen 19-9 kinetics, and tolerability/safety. The study is currently enrolling. Clinical trial information: NCT07259317 .
Borazanci et al. (Thu,) studied this question.