| 📌 The essentials On March 25, 2026, the FDA approved Lifyorli (relacorilant, Corcept Therapeutics) in combination with nab-paclitaxel for adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab. This is a full approval based on overall survival data, not accelerated approval. The mechanism: relacorilant is an oral, selective glucocorticoid receptor (GR) antagonist. It blocks cortisol’s tumor-protective action that suppresses apoptosis in cancer cells, sensitizing them to nab-paclitaxel’s cytotoxic effect. Dosing: relacorilant 150 mg orally on the day before, day of, and day after each nab-paclitaxel infusion, given in 28-day cycles. The clinical basis: Phase 3 ROSELLA trial (NCT05257408), published in The Lancet, showing median overall survival of 16.0 versus 11.9 months (HR 0.65; p=0.0004), a 35% reduction in risk of death. The 18-month OS rate was 46% versus 27%. NCCN has designated relacorilant plus nab-paclitaxel as a preferred regimen for platinum-resistant ovarian cancer. |
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For roughly thirty years, the story of platinum-resistant ovarian cancer has been one of persistent failure. Trial after trial. Checkpoint inhibitor after checkpoint inhibitor. PARP inhibitor combinations. Antibody-drug conjugates. Antiangiogenics beyond bevacizumab. The disease has resisted almost everything, and the graveyard of Phase 3 trials that failed in this setting is long and dispiriting.
Platinum-resistant ovarian cancer is defined by a clinical reality: the cancer progresses within six months of completing platinum-based chemotherapy. At that point, the treatment options narrow sharply. Single-agent non-platinum chemotherapy, including pegylated liposomal doxorubicin, paclitaxel, gemcitabine, and topotecan, with or without bevacizumab, has been the mainstay. Response rates are modest. Survival is poor.
On March 25, 2026, the FDA approved Lifyorli (relacorilant) in combination with nab-paclitaxel for adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is the first FDA-approved selective glucocorticoid receptor antagonist, a category of drug that does not target the tumor directly, but instead targets the role cortisol plays in helping tumors resist the chemotherapy meant to kill them. The pivotal ROSELLA trial, published simultaneously in The Lancet, delivered something this disease has not seen in a long time: a statistically robust overall survival improvement.
The Disease: Why Platinum-Resistant Ovarian Cancer Is So Hard to Treat
Ovarian cancer is the most lethal gynecologic malignancy. In 2024, an estimated 320,000 new cases were diagnosed globally and approximately 210,000 women died from the disease, accounting for about 4.8% of all cancer-related mortality. In the United States, ovarian cancer kills approximately 12,800 women annually. The high mortality relative to incidence reflects a disease that is typically diagnosed at advanced stage (III or IV), when cure is unlikely.
Platinum-based chemotherapy, carboplatin and cisplatin, has been the backbone of ovarian cancer treatment for three decades. Most patients initially respond well. The problem is recurrence: approximately 70% of patients with advanced ovarian cancer will relapse, and through successive platinum cycles, resistance becomes inevitable. Once a patient’s cancer progresses within six months of the last platinum regimen, they are classified as platinum-resistant, and the therapeutic landscape changes dramatically for the worse.
| Why this setting has been so difficult: the failed trials The list of Phase 3 trials that failed to improve overall survival in platinum-resistant ovarian cancer is extensive. Checkpoint inhibitors have largely disappointed in ovarian cancer despite transforming outcomes in melanoma, lung cancer, and other solid tumors. The ARTISTRY-7 trial, evaluating nemvaleukin plus pembrolizumab versus chemotherapy, was negative. The underlying biology is partially explanatory: ovarian tumors often have immunosuppressive microenvironments with low T-cell infiltration, limited PD-L1 expression, and mechanisms that actively exclude immune cells. Notably, the ENGOT-ov65/KEYNOTE-B96 trial of pembrolizumab plus paclitaxel plus or minus bevacizumab in platinum-resistant ovarian cancer did ultimately produce the first significant PFS and OS benefit with immunotherapy in this setting. That approval, covered here on Health Evidence Digest, required PD-L1 CPS of 1 or higher for the indicated population. For patients who do not meet that biomarker threshold or who have progressed after immunotherapy, the unmet need remained enormous. What was needed for that broader population was a different angle of attack entirely. |
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The Mechanism: Cortisol as a Shield for Tumor Cells
The biological rationale for relacorilant starts with a question that oncologists have long observed but had limited tools to address: why does chemotherapy work initially in ovarian cancer, then stop working? Part of the answer involves the tumor microenvironment, and specifically the role cortisol plays within it.
Cortisol is a glucocorticoid hormone produced by the adrenal glands that regulates stress responses, inflammation, and immune function. In normal physiology, cortisol plays many important and beneficial roles. In tumor biology, however, cortisol, acting through the glucocorticoid receptor (GR) expressed in many cancer cell types, contributes to chemotherapy resistance through a specific and well-characterized mechanism: it inhibits apoptosis.
Apoptosis is programmed cell death, the cellular self-destruct mechanism that chemotherapy is specifically designed to trigger. Taxane chemotherapies like nab-paclitaxel work by disrupting microtubule function during cell division, causing mitotic arrest and ultimately apoptotic cell death. When cortisol activates GR signaling in tumor cells, it suppresses the apoptotic machinery, effectively giving those cells a cortisol-mediated shield against the chemotherapy that should be killing them.
Relacorilant is an oral, selective glucocorticoid receptor antagonist. It competes with cortisol at the GR binding site, blocking the receptor without activating it. With GR signaling suppressed, cortisol’s protection of tumor cells from apoptosis is reduced, and the tumor cells become more sensitive to nab-paclitaxel’s intended mechanism. Relacorilant is selective: it binds only to the glucocorticoid receptor, not to the progesterone, androgen, mineralocorticoid, or estrogen receptors. This selectivity is what distinguishes it from older, non-selective glucocorticoid antagonists like mifepristone.
| The dosing schedule and why it matters for tolerability Relacorilant is taken orally at 150 mg on three specific days per 28-day cycle: the day before each nab-paclitaxel infusion, the day of the infusion, and the day after. Nab-paclitaxel is administered intravenously on days 1, 8, and 15 of each cycle. This intermittent dosing design is intentional. Continuous glucocorticoid receptor blockade would interfere with the body’s normal cortisol-dependent functions, including immune regulation, glucose metabolism, and stress response. By limiting GR blockade to the three days surrounding each chemotherapy infusion, the regimen specifically targets the period when cortisol’s tumor-protective effects are most relevant, while minimizing disruption to normal physiology. This design choice is supported by the trial’s safety data: no cases of adrenal insufficiency were reported in the ROSELLA trial. |
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The ROSELLA Trial: Design and Full Results
The Phase 3 ROSELLA trial (NCT05257408) was an international, randomized, controlled, open-label study conducted across 117 sites in 14 countries, including the United States, multiple European nations, South Korea, Brazil, Argentina, Canada, and Australia, in collaboration with the GOG Foundation, ENGOT, APGOT, LACOG, and ANZGOG. Enrollment ran from January 2023 to April 2024.
Patient population
Eligible patients were adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, defined as disease progression within six months of the last platinum-based therapy. All had received one to three prior systemic therapy regimens, and all had prior bevacizumab exposure. Patients requiring chronic corticosteroids were excluded. The median patient age was 61 to 62 years.
Randomization and treatment
381 patients were randomized 1:1 to relacorilant 150 mg plus nab-paclitaxel 80 mg/m² (n=188), or nab-paclitaxel alone at 100 mg/m² (n=193). The monotherapy arm received a higher dose of nab-paclitaxel to reflect the absence of a chemo-sensitizing partner. The dual primary endpoints were progression-free survival (PFS) by RECIST 1.1 and blinded independent central review, and overall survival.
Results
| Endpoint | Relacorilant plus nab-paclitaxel | Nab-paclitaxel alone |
|---|---|---|
| Median overall survival | 16.0 months (95% CI 13.0 to 18.3) | 11.9 months (95% CI 10.0 to 13.8) |
| OS hazard ratio | 0.65 (95% CI 0.51 to 0.83) | Reference |
| OS p-value | 0.0004 | — |
| Reduction in risk of death | 35% | — |
| 12-month OS rate | 60% | 50% |
| 18-month OS rate | 46% | 27% |
| Median PFS (BICR) | 6.5 months (95% CI 5.6 to 7.4) | 5.5 months (95% CI 3.9 to 5.9) |
| PFS hazard ratio | 0.70 (95% CI 0.54 to 0.91) | Reference |
| PFS p-value | 0.0076 | — |
| Reduction in risk of progression | 30% | — |
| 12-month PFS rate | 25% | 13% |
| Second PFS (PFS2) hazard ratio | 0.73 (p=0.0037) | Reference |
Source: Olawaiye AB et al. The Lancet. 2026. doi:10.1016/S0140-6736(26)00462-9. ROSELLA trial (NCT05257408).
The OS data maturity at the final analysis was 76%, meaning three-quarters of patients had experienced the endpoint, making this a robust and interpretable dataset. The Lancet publication notes that the Kaplan-Meier survival curves show progressively widening separation over time, suggesting durable benefit rather than early separation that converges. The 18-month OS rate difference — 46% versus 27% — is particularly striking: at 18 months, nearly half of patients on the combination were still alive, compared with just over one-quarter on chemotherapy alone.
The benefit was consistent across all prespecified subgroups, including patients who had received two versus three prior lines of therapy, those with prior PARP inhibitor exposure, and across geographic regions. No biomarker selection was required for eligibility or benefit, which means the improvement applies to the broad platinum-resistant ovarian cancer population, not a molecularly defined subset.
The principal investigator of the ROSELLA trial, Dr. Alexander B. Olawaiye, MD, Director of Gynecologic Cancer Research at Magee-Womens Hospital of UPMC, characterized the finding at the SGO Late-Breaker presentation as the first demonstration that modulating the steroid receptor pathway, specifically the glucocorticoid receptor, can produce benefit in the treatment of platinum-resistant ovarian cancer, noting that the uniqueness of the pathway makes this new in every way.
Safety: What the Data Shows
The combination arm had a higher rate of grade 3 or higher treatment-emergent adverse events than the monotherapy arm: 74.5% versus 59.5%. The primary driver was hematologic toxicity, particularly neutropenia (44% versus 25% in the combination arm) and anemia (18% versus 9%). These findings reflect the addition of any chemotherapy-sensitizing agent and are consistent with what clinicians encounter in other combination regimens.
| Adverse event (20% or higher incidence) | Combination arm | Monotherapy arm |
|---|---|---|
| Decreased hemoglobin | Most common, all grades | Lower rate |
| Neutropenia (grade 3 or higher) | 44% | 25% |
| Fatigue | 20% or higher | Present |
| Nausea | 20% or higher | Present |
| Diarrhea | 20% or higher | Present |
| Decreased platelets | 20% or higher | Present |
| Rash | 20% or higher | Present |
| Decreased appetite | 20% or higher | Present |
| Anemia (grade 3 or higher) | 18% | 9% |
| Adrenal insufficiency | 0 cases | 0 cases |
| Deaths attributed to relacorilant | 0 | 0 |
Two specific safety findings deserve emphasis. First, no cases of adrenal insufficiency were observed, validating the intermittent dosing design. Second, peripheral neuropathy, a known concern with taxane chemotherapy, occurred at similar rates in both arms, suggesting relacorilant did not worsen this chemotherapy-related toxicity.
The prescribing label carries a contraindication for patients who require corticosteroids for a life-saving indication, because GR blockade would impair their effectiveness. Patients on systemic corticosteroids for severe asthma, inflammatory bowel disease, or immunosuppression following transplant require careful evaluation before initiating Lifyorli. Prescribing information warnings include neutropenia and severe infection risk, adrenal insufficiency monitoring, exacerbation of conditions treated with glucocorticoids, and embryo-fetal toxicity.
What This Approval Represents
The NCCN Clinical Practice Guidelines in Oncology added Lifyorli plus nab-paclitaxel as a preferred regimen for platinum-resistant ovarian cancer following the approval. That designation reflects the committee’s assessment that the overall survival data from ROSELLA represents a meaningful advance for a patient population with very limited meaningful advances over the past decade.
Three aspects of the ROSELLA data deserve specific emphasis as markers of robustness. The OS analysis is mature: 76% data maturity is high for an ongoing survival analysis and ensures the hazard ratio estimate is reliable. Subsequent therapies were balanced between the two arms, ruling out the possibility that post-progression treatment differences explain the survival benefit. And the benefit was consistent across all predefined subgroups, including those heavily pretreated and those with prior PARP inhibitor exposure.
| What we do not yet know: open questions for clinical practice No biomarker predicted response. ROSELLA enrolled without biomarker selection and found benefit across all subgroups. That is good news for broad access, but it means there is not yet a way to identify which patients are most likely to respond, or whether some patients have particularly high GR expression that drives greater benefit. Corcept and academic collaborators are likely studying this as a post-approval research question. Patient-reported quality of life. The ROSELLA trial included EORTC quality-of-life measures as secondary endpoints. Full patient-reported outcome analysis had not been comprehensively presented at time of writing. For patients in this setting, tolerability and quality of remaining life matter alongside survival data. Relacorilant in other tumor types. Corcept has active or planned trials of relacorilant in platinum-sensitive ovarian cancer, endometrial cancer, cervical cancer, pancreatic cancer, and prostate cancer. The proof-of-concept from ROSELLA that GR antagonism can sensitize tumors to chemotherapy may accelerate these programs. |
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Regulatory Status and Access
FDA approval
Approved March 25, 2026, for adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens, at least one of which included bevacizumab. This is a full approval, based on overall survival data from ROSELLA meeting both co-primary endpoints.
European Medicines Agency
Corcept has submitted a Marketing Authorisation Application (MAA) to the EMA for relacorilant in platinum-resistant ovarian cancer. Relacorilant has received orphan drug designation from the European Commission for ovarian cancer treatment. The EMA review is ongoing.
Patient support
Corcept has established Lifyorli Support for patients and healthcare providers at 1-855-439-6754 (1-85-LIFYORLI). For questions about eligibility, prior authorization support, or financial assistance programs, this is the recommended first contact.
For patients and families navigating platinum-resistant ovarian cancer, the Ovarian Cancer Research Alliance and the Foundation for Women’s Cancer both maintain updated treatment information, clinical trial directories, and peer support resources. For related HED coverage of ovarian cancer treatment advances in 2026, see our post on pembrolizumab becoming the first approved immunotherapy for platinum-resistant ovarian cancer and our analysis of vepdegestrant and the PROTAC mechanism in breast cancer as examples of how novel mechanisms of action are reshaping gynecologic and breast oncology in the same period.
Sources
Corcept press release (approval): FDA Approves Corcept’s Selective Glucocorticoid Receptor Antagonist. ir.corcept.com. March 25, 2026.
Corcept press release (SGO/OS data): Corcept Presents Complete Data from Pivotal ROSELLA Trial in SGO Late-Breaker with Simultaneous Publication in The Lancet. ir.corcept.com. April 10, 2026.
ROSELLA trial registration: NCT05257408. ClinicalTrials.gov.
CancerNetwork OS coverage: Relacorilant/Nab-Paclitaxel Reduces Risk of Death by 35% in Platinum-Resistant Ovarian Cancer. cancernetwork.com. April 2026.
CURE coverage: Lifyorli Combo Approved in Platinum-Resistant Ovarian Cancer. curetoday.com. March 2026.
Targeted Oncology: Relacorilant Demonstrates Significant OS in Platinum-Resistant Ovarian Cancer. targetedonc.com. April 2026.
PROC treatment landscape: Current Treatments, Future Strategies for Platinum-Resistant Ovarian Cancer. AJMC. March 2026.
PROC unmet need review: Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum Resistance. PubMed. 2023. PMID:37079311.
NCCN guidelines: Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. NCCN.
Glucocorticoid receptor biology: Glucocorticoid Receptor Signaling in Cancer. PMC7694440.
Apoptosis reference: Apoptosis. StatPearls. NCBI.
Cortisol overview: Cortisol. StatPearls. NCBI.
RECIST/PFS methodology: New Response Evaluation Criteria in Solid Tumours. PMC3107543.
Checkpoint inhibitors in ovarian cancer: Immune Checkpoint Inhibitors in Ovarian Cancer. PMC7174922.
PARP inhibitors: PARP Inhibitors. cancer.gov.
Neutropenia: Neutropenia. StatPearls. NCBI.
Patient resources: Ovarian Cancer Research Alliance | Foundation for Women’s Cancer | NCCN Ovarian Cancer Guidelines | Lifyorli Support: 1-855-439-6754
| Disclaimer: Health Evidence Digest provides general information about FDA approvals and health research for educational purposes. This content is not a substitute for professional medical advice, diagnosis, or treatment. Treatment decisions for platinum-resistant ovarian cancer should be made in consultation with a qualified gynecologic oncologist. |
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