TRIDENT: A phase 2 study of relacorilant plus nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic ductal adenocarcinoma.

Abstract

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 .