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DRUG:

relacorilant (CORT125134)

i
Other names: CORT125134, CORT-125134, CORT 125134
Company:
Corcept Therap
Drug class:
GCR antagonist
3d
GRADIENT: Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (clinicaltrials.gov)
P3, N=137, Completed, Corcept Therapeutics | Active, not recruiting --> Completed
Trial completion
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relacorilant (CORT125134)
7d
New Trends in Treating Cushing's Disease. (PubMed, touchREV Endocrinol)
At the pituitary level, pasireotide is an approved somatostatin receptor ligand, and compounds targeting cell cycle regulation, cell signalling and epigenetics are now under investigation. Levoketoconazole and osilodrostat are novel steroid inhibitors, and relacorilant overcomes the adverse effects of mifepristone. Adrenal ACTH receptor blockage and immunotherapy could also play a role.
Journal
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SSTR (Somatostatin Receptor)
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relacorilant (CORT125134) • Signifor (pasireotide) • Mifeprex (mifepristone)
4ms
ROSELLA: Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer (clinicaltrials.gov)
P3, N=360, Active, not recruiting, Corcept Therapeutics | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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albumin-bound paclitaxel • relacorilant (CORT125134)
4ms
Study of Drug 1 (Enzalutamide) Plus Drug 2 (Relacorilant) for Patients With Prostate Cancer (clinicaltrials.gov)
P1, N=35, Active, not recruiting, University of Chicago | Recruiting --> Active, not recruiting | N=24 --> 35
Enrollment closed • Enrollment change • Metastases
|
Xtandi (enzalutamide capsule) • relacorilant (CORT125134)
5ms
GRADIENT: Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (clinicaltrials.gov)
P3, N=130, Active, not recruiting, Corcept Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024
Enrollment closed • Trial completion date • Trial primary completion date
|
relacorilant (CORT125134)
7ms
Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome (clinicaltrials.gov)
P2, N=75, Enrolling by invitation, Corcept Therapeutics | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
|
relacorilant (CORT125134)
7ms
GRACE: A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome (clinicaltrials.gov)
P3, N=152, Completed, Corcept Therapeutics | Active, not recruiting --> Completed
Trial completion
|
relacorilant (CORT125134)
8ms
Enrollment open
|
Xtandi (enzalutamide capsule) • relacorilant (CORT125134)
8ms
Enrollment closed • Combination therapy • Metastases
|
albumin-bound paclitaxel • relacorilant (CORT125134)
9ms
GRADIENT: Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas (clinicaltrials.gov)
P3, N=130, Recruiting, Corcept Therapeutics | Trial completion date: Oct 2023 --> Mar 2024 | Trial primary completion date: Oct 2023 --> Mar 2024
Trial completion date • Trial primary completion date
|
relacorilant (CORT125134)
9ms
Trial completion • Enrollment change • Combination therapy
|
Keytruda (pembrolizumab) • relacorilant (CORT125134)
11ms
Trial completion date • Trial primary completion date
|
relacorilant (CORT125134)
11ms
Trial completion date • Trial primary completion date
|
relacorilant (CORT125134)
12ms
Phase classification
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Keytruda (pembrolizumab) • relacorilant (CORT125134)
12ms
Trial completion date • Trial primary completion date
|
albumin-bound paclitaxel • relacorilant (CORT125134)
1year
New P1 trial
|
relacorilant (CORT125134)
1year
New P1 trial
|
relacorilant (CORT125134)
1year
New P1 trial
|
relacorilant (CORT125134)
1year
New P1 trial
|
relacorilant (CORT125134)
1year
Glucocorticoid Receptor Regulates and Interacts with LEDGF/p75 to Promote Docetaxel Resistance in Prostate Cancer Cells. (PubMed, Cells)
GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression...The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR-LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.
Journal
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PSIP1 (PC4 And SFRS1 Interacting Protein 1) • NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1)
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PSIP1 expression
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docetaxel • Xtandi (enzalutamide capsule) • relacorilant (CORT125134) • exicorilant (CORT125281)
over1year
ROSELLA (GOG-3073, ENGOT-Ov72/MITO): A Phase 3 Study Of Relacorilant + Nab-Paclitaxel Vs. Nab-Paclitaxel In Advanced, Platinum-Resistant Ovarian Cancer (ESGO 2023)
Women with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer who have received 1â3 lines of prior systemic anticancer therapy, including prior bevacizumab, and at least 1 line of platinum-based therapy are being enrolled. Results The primary endpoint is PFS assessed by blinded independent central review. Key secondary endpoints include OS, PFS by investigator assessment, objective response rate, best overall response, DoR, safety, pharmacokinetics, pharmacodynamics, patient-reported outcomes, and quality of life.Conclusion N/A
P3 data • Metastases
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NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1)
|
Avastin (bevacizumab) • albumin-bound paclitaxel • relacorilant (CORT125134)
over1year
Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study. (PubMed, J Clin Oncol)
Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).
P2 data • Journal
|
albumin-bound paclitaxel • relacorilant (CORT125134)
over1year
Osilodrostat as an Emergency Alternative for Hypercortisolism in a Patient With an Impaired Liver Function. (ENDO 2023)
Due to elevated liver functiontests, the patient couldn't have started ketoconazole and relacorilant treatment.Because of non-controlled DM, pasireotide treatment was contraindicated in her case.She didn't agree either for metyrapone treatment or for adrenalectomy. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*
Clinical
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relacorilant (CORT125134) • Signifor (pasireotide)
over1year
Selective glucocorticoid receptor modulation reveals a new role for CLEC10A in patients with solid tumors (AACR 2023)
In a randomized, controlled phase 2 study in patients with recurrent, platinum-resistant ovarian cancer (NCT03776812), gene changes were assessed in 139 patients after treatment with relacorilant + nab-paclitaxel (NP) or NP alone. CLEC10A and the genes correlated with its expression were found to be primarily expressed by a specific subset of dendritic cells, supporting previous reports that GR agonism can suppress dendritic cells. This analysis of CLEC10A and other identified GR target genes confirmed that systemic GR activity in patients with a range of solid tumors can be modulated pharmacologically, indicates that GR modulation may be associated with survival in patients with ovarian cancer, and provides new insights into the systemic functions of the GR in humans.
Clinical • IO biomarker
|
TNFRSF17 (TNF Receptor Superfamily Member 17) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CCR2 (C-C Motif Chemokine Receptor 2) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • FPR3 (Formyl Peptide Receptor 3)
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albumin-bound paclitaxel • relacorilant (CORT125134)
almost2years
GENETICALLY ENGINEERED HUMAN PITUITARY CORTICOTROPH TUMOR ORGANOIDS EXHIBIT DIVERGENT RESPONSES TO GLUCOCORTICOID RECEPTOR MODULATORS. (PubMed, Transl Res)
Relacorilant sensitized PitNET organoid responsiveness to Pasireotide. Therefore, our study identified the potential therapeutic use of relacorilant in combination with somatostatin analogs and demonstrated the advantages of relacorilant over Mifepristone, supporting its further development for use in the treatment of CD patients.
Journal
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SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2) • SSTR5 (Somatostatin Receptor 5)
|
SSTR2 expression • SSTR5 expression
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relacorilant (CORT125134) • Signifor (pasireotide) • Korlym (mifepristone) • Mifeprex (mifepristone)
over2years
Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant. (PubMed, Front Endocrinol (Lausanne))
Glucocorticoid receptor (GR) antagonism with mifepristone has been shown to reverse the glucocorticoid-induced downregulation of SSTR2; however, the effects of GR modulation on SSTR2 expression in ACTH-secreting NETs, particularly corticotroph pituitary tumors, are not well known...Based on these findings, we propose that GR modulation in patients with ACTH-secreting NETs upregulates previously suppressed SSTR2s, resulting in tumor-specific antisecretory and anti-proliferative effects. The effect of relacorilant on pituitary corticotroph tumors is being investigated in an ongoing phase 3 study (NCT03697109; EudraCT 2018-003096-35).
Journal
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SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
|
SSTR2 expression • SSTR Expression
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relacorilant (CORT125134) • Korlym (mifepristone) • Mifeprex (mifepristone)
over3years
Adrenal tumors provide insight into the role of cortisol in NK cell activity. (PubMed, Endocr Relat Cancer)
Thus, GR antagonism may increase the abundance and function of NK and other immune cells in the tumor microenvironment, promoting immune response in GC+ ACC and other malignancies with GC+. This hypothesis will be tested in a phase 1 trial of relacorilant + ICI.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
|
relacorilant (CORT125134)
over3years
Emerging drugs for the treatment of Adrenocortical Carcinoma. (PubMed, Expert Opin Emerg Drugs)
Data of immune checkpoint blockade with nivolumab, ipilimumab, pembrolizumab and avelumab is explored in detail...Progress in the treatment of ACC has faced challenges stemming from the rarity of the disease. Given recent advances in the understanding of the molecular pathogenesis of ACC, a window of opportunity has now opened to make significant progress in developing therapeutic options that target key pathways such as excessive glucocorticoid signaling, WNT signaling, cell cycle and immune checkpoints.
Journal
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EGFR (Epidermal growth factor receptor)
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • Bavencio (avelumab) • relacorilant (CORT125134)
over4years
Clinical • Enrollment closed • Combination therapy
|
MUC16 (Mucin 16, Cell Surface Associated)
|
albumin-bound paclitaxel • relacorilant (CORT125134)
over4years
[VIRTUAL] Suppression of tumor immune activity in adrenocortical carcinoma with excess glucocorticoid (AACR-II 2020)
Reduced abundance of immune cells and immune-related transcripts in GC+ ACC provides insight into the mechanisms by which GC may limit response to ICI therapy. GR antagonism may increase immune related transcripts, thus promoting tumor immune response in GC+ ACC and other malignancies with elevated GC activity. This hypothesis will be tested in a Phase 1 trial of relacorilant + ICI.
Late-breaking abstract • Tumor Mutational Burden • IO biomarker
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TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
|
relacorilant (CORT125134)
over4years
[VIRTUAL] Impact of relacorilant, a selective glucocorticoid receptor antagonist, on the immunosuppressive effects of endogenous cortisol. (ASCO 2020)
In patients with advanced solid tumors, relacorilant + nab-paclitaxel systemically suppressed the expression of canonical GR-controlled genes (ptgs2 P< .001) and genes encoding candidate-immunomodulatory drug targets (cxcl8, ptger4, ido1; P< .001). Evidence of T-cell activation by relacorilant was observed in PBMCs, syngeneic mouse tumors, and patients with sustained response in a Phase 1 study. This supports the hypothesis that relacorilant can reverse immune suppression by endogenous cortisol in solid tumor cancers. Clinical studies with immune checkpoint inhibitors and relacorilant are planned.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IDO1 (Indoleamine 2,3-dioxygenase 1) • IL10 (Interleukin 10) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
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albumin-bound paclitaxel • relacorilant (CORT125134)