Researchers have developed an experimental drug that helps overcome a key defense mechanism cancer cells use to survive chemotherapy. The compound, called relacorilant, blocks the effects of the stress hormone cortisol, effectively disabling a protective shield that cancer cells deploy to resist treatment. In a pivotal Phase 3 clinical trial, the drug demonstrated significant survival benefits for women with platinum-resistant ovarian cancer, one of the most difficult-to-treat gynecologic cancers.
The new approach marks a potential paradigm shift in cancer therapy by targeting the hormonal environment that shelters tumor cells rather than attacking the cells directly. By neutralizing the protective effects of cortisol, relacorilant sensitizes cancer cells to the lethal impact of chemotherapy, making standard treatments more effective. The findings from the ROSELLA trial suggest that this method could extend the lives of patients who have exhausted many other options and may offer a new strategy for combating treatment resistance across a variety of cancers.
The Cortisol Shield
Cancer cells often co-opt the body’s natural stress response to survive the harsh environment created by chemotherapy. When the body is under stress, it releases cortisol, a hormone that regulates a wide range of processes to help the body cope. In the context of cancer, this hormone can inadvertently help tumor cells by inhibiting apoptosis, the process of programmed cell death that chemotherapy is designed to induce. This cortisol-driven mechanism acts as a protective shield, allowing cancerous cells to withstand chemical assaults and continue to proliferate.
This resistance is a primary reason why treatments that are initially effective can stop working. In platinum-resistant ovarian cancer, this challenge is particularly acute. The condition, which affects about 20,000 women in the U.S. annually, is defined by the cancer recurring within six months of treatment with powerful platinum-based chemotherapy drugs. Once this resistance develops, patients face a grim prognosis, with subsequent treatments offering only modest benefits.
A Novel Mechanism of Action
The experimental drug relacorilant was developed by Corcept Therapeutics, a biopharmaceutical firm that has researched cortisol modulation for over two decades. Relacorilant is a selective glucocorticoid receptor antagonist. It works by binding to the receptors that cortisol would normally attach to, effectively blocking the hormone’s signal from ever reaching the cancer cell. Without the pro-survival signal from cortisol, the cancer cells become vulnerable to chemotherapy once again.
This strategy is fundamentally different from most cancer drug development, which focuses on creating more potent toxins or targeting specific mutations within the tumor. Instead of adding a new weapon, relacorilant sharpens an existing one. Because cortisol-mediated resistance is not unique to ovarian tumors, this approach could potentially be used as a platform to enhance chemotherapy’s effectiveness against a wide range of cancers, including prostate cancer, where it is also being studied.
Clinical Trial Breakthrough
Methods and Results
The pivotal Phase 3 ROSELLA trial evaluated the effectiveness of relacorilant in patients with platinum-resistant ovarian cancer. Participants were given the chemotherapy agent nab-paclitaxel, with one group also receiving relacorilant and a control group receiving chemotherapy alone. The late-breaking data, scheduled for presentation at the American Society of Clinical Oncology Annual Meeting, revealed a significant improvement for the combination therapy group.
Patients receiving relacorilant alongside chemotherapy had a 30% lower risk of disease progression or death compared to those on chemotherapy alone. The median progression-free survival—the length of time patients lived without their cancer getting worse—was 6.5 months for the combination group, compared to 5.5 months for the monotherapy group. More significantly, interim data on overall survival showed that the relacorilant combination extended life expectancy by 4.5 months, with a median survival of 16 months versus 11.5 months for chemotherapy alone. This represents a 31% reduction in the risk of death.
Context and Significance
For a patient population with very few effective options, these results are highly meaningful. Standard single-agent chemotherapies for platinum-resistant ovarian cancer typically yield progression-free survival of only about three months. While a one-month improvement in progression-free survival may seem modest, the 4.5-month gain in overall survival is considered a substantial clinical benefit and could drive adoption of the new regimen. This result is comparable to the survival benefit seen with recently approved antibody-drug conjugates, but with the potential for broader applicability since it does not depend on specific biomarkers like folate receptor alpha expression.
The Path to Market
Following the successful trial results, Corcept plans to submit a New Drug Application to the U.S. Food and Drug Administration in the third quarter of 2025. A subsequent application for marketing authorization in Europe will follow. The company’s orphan drug designation for this indication may help expedite regulatory review. However, the drug will face scrutiny from payers, who will weigh the clinical benefit against the cost. Health technology bodies have become increasingly critical of the high price of new cancer therapies, and the modest one-month gain in progression-free survival may be a point of contention.
Despite these hurdles, the strong overall survival data and the novel mechanism of action have generated positive attention. Wall Street analysts have noted the drug’s potential, and the company’s stock rose following the announcement of the trial results. The success of relacorilant not only offers a new lifeline for ovarian cancer patients but also validates the broader therapeutic strategy of targeting cortisol modulation as a way to overcome treatment resistance.