Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines. PATIENTS AND METHODS: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles. The primary efficacy endpoint was objective response rate (ORR) by blinded independent central review. Progression-free survival (PFS), overall survival (OS), target gene modulation, and safety were also assessed. RESULTS: Of 43 patients enrolled, 31 were evaluable for ORR (12 did not reach first postbaseline radiographic assessment). An interim analysis to assess whether ORR was ≥10% showed no confirmed responses and the study was discontinued. Two (6.5%) patients attained unconfirmed partial responses and 15 (48.4%) had stable disease. Fourteen of 31 (45.2%) patients had reductions in target lesion size, despite prior nab-paclitaxel exposure in 12 of the 14. Median PFS and OS were 2.4 months (95% CI, 1.4-4.2) and 3.9 months (95% CI, 2.8-4.9), respectively. The most common adverse events were fatigue and nausea. RNA analysis confirmed that relacorilant plus nab-paclitaxel suppressed 8 cortisol target genes of interest. CONCLUSION: Relacorilant plus nab-paclitaxel showed modest antitumor activity in heavily pretreated patients with mPDAC, with no new safety signals. Studies of this combination in other indications with a high unmet medical need are ongoing.
Source: The Oncologist
Authors: Erkut H Borazanci, Nathan Bahary, Vincent Chung, Timothy K Huyck, Ebenezer A Kio, Elena Gabriela Chiorean, Roland T Skeel, Olatunji B Alese, Dana B Cardin, Christos Fountzilas, Wahid T Hanna, Alexis D Leal, Valerie Lee, Anne M Noonan, Philip A Philip, Zev A Wainberg, Hristina Pashova, Grace Mann, Paul E Oberstein
Institutions: HonorHealth, Allegheny Health Network, City Of Hope National Medical Center, City of Hope, Nebraska Cancer Specialists, Goshen Health, University of Washington, Fred Hutch Cancer Center, University of Toledo Medical Center, Emory University, Winship Cancer Institute, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Roswell Park Comprehensive Cancer Center, University of Tennessee at Knoxville, University of Colorado Anschutz, Johns Hopkins University, The Ohio State University, Wayne State University, The Barbara Ann Karmanos Cancer Institute, University of California, Los Angeles, Corcept Therapeutics (United States), NYU Langone Health, New York University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,045
Funder: National Cancer Institute
Award: Cancer Center Support Grant
OpenAlex ID: W4401933428