ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Phase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Novel Therapeutic Strategies for Metastatic Prostate Cancer Care.European urology · 2025Pooled it
- Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer.Cancer research · 2026Review
- Targeting the NR3C1-ACSL4 Axis Triggers Ferroptosis to Overcome Radioresistance in Prostate Cancer.Cancer science · 2026Article
- TMPRSS2-ERG confers resistance of prostate cancer to antiandrogens.EMBO molecular medicine · 2026Article
- High level expression of glucocorticoid receptor (GR) is linked to aggressive tumor features, early biochemical recurrence, and genetic instability in prostate cancer.Prostate cancer and prostatic diseases · 2026Article
- Transcription Factors and Methods for the Pharmacological Correction of Their Activity.International journal of molecular sciences · 2025Review
- A TBX2-driven signaling switch from androgen receptor to glucocorticoid receptor confers therapeutic resistance in prostate cancer.Oncogene · 2025Article
- The future of androgen receptor targeting in prostate cancer: third-generation inhibitors and beyond.Therapeutic advances in medical oncology · 2025Review
- ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.Cancer research communications · 2024Article
- Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators.Cell death & disease · 2024Article
- Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.Journal of experimental & clinical cancer research : CR · 2024Article
- A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Glucocorticoid receptor action in prostate cancer: the role of transcription factor crosstalk.Frontiers in endocrinology · 2024Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
purposeIncreased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist. PATIENTS AND
methodsSafety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase 2 dose (RP2D).
resultsA total of 41 patients were enrolled. There were no dose-limiting toxicities and the RP2D was selected as 240 mg of ORIC-101 and 160 mg of enzalutamide daily. At the RP2D, the most common treatment-related adverse events were fatigue (38.7%), nausea (29.0%), decreased appetite (19.4%), and constipation (12.9%). Pharmacokinetic/pharmacodynamic data confirmed ORIC-101 achieved exposures necessary for GR target engagement. Overall, for 31 patients treated at the RP2D, there was insufficient clinical benefit based on DCR (25.8%; 80% confidence interval: 15.65-38.52) which did not meet the prespecified target rate, leading to termination of the study. Exploratory subgroup analyses based on baseline GR expression, presence of AR resistance variants, and molecular features of aggressive variant prostate cancer suggested possible benefit in patients with high GR expression and no other resistance markers, although this would require confirmation.
conclusionsAlthough the combination of ORIC-101 and enzalutamide demonstrated an acceptable tolerability profile, GR target inhibition with ORIC-101 did not produce clinical benefit in men with metastatic prostate cancer resistant to enzalutamide.
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