Lifyorli (Relacorilant) Combo FDA-Approved for Platinum-Resistant Ovarian Cancer

The FDA has approved Lifyorli (relacorilant) to be used with nab-paclitaxel for adults with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have had one to three previous systemic therapies, including bevacizumab.

This approval adds a new treatment option for patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Relacorilant is a glucocorticoid receptor antagonist developed by Corcept Therapeutics, a company focused on treatments that modulate cortisol activity in cancer and other disease areas.

Platinum-resistant ovarian cancer refers to disease that returns within six months after platinum-based chemotherapy, the usual first-line treatment. These tumors are more difficult to treat because they no longer respond well to standard platinum drugs and are associated with limited therapeutic options.

Relacorilant is a small oral molecule that targets the glucocorticoid receptor, which is influenced by the hormone cortisol. Cortisol can lessen the effectiveness of chemotherapy by inhibiting apoptosis, the process through which cancer cells die. By blocking this pathway, relacorilant is designed to improve the activity of chemotherapy drugs such as nab-paclitaxel.

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The FDA’s decision was based on results from the Phase III ROSELLA trial. This multicenter, open-label study enrolled 381 patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Participants had received up to three prior lines of systemic therapy, and prior bevacizumab treatment was required. No biomarker selection was required.

Patients were randomized in a 1:1 ratio to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone.

The trial met its dual primary endpoints of progression-free survival (PFS) and overall survival (OS). Patients who received relacorilant with nab-paclitaxel experienced a median of 6.5 months without their cancer worsening, compared to 5.5 months for those who received nab-paclitaxel alone. This corresponded to a 30% reduction in the risk of disease progression or death (hazard ratio 0.70; p=0.0076).

Patients in the combination group also lived longer overall, with a median survival of 16.0 months compared to 11.9 months in the control group. This represented a 35% reduction in the risk of death (hazard ratio 0.65; p=0.0004).

Progression-free survival measures how long a patient lives without the cancer worsening, while overall survival measures how long patients live after treatment begins.

Relacorilant is taken by mouth once daily for three days around each chemotherapy infusion. Nab-paclitaxel is administered intravenously on Days 1, 8 and 15 of a 28-day cycle, continuing until the disease progresses or side effects become difficult to manage.

Relacorilant is the first FDA-approved selective glucocorticoid receptor antagonist for this indication.

Corcept is also evaluating relacorilant across multiple tumor types, including endometrial, cervical, pancreatic and prostate cancers. Additional data are expected from ongoing studies such as the BELLA trial in ovarian cancer. The company has submitted a Marketing Authorisation Application to the European Medicines Agency (EMA) for relacorilant in platinum-resistant ovarian cancer.

Other treatment approaches are also being evaluated in platinum-resistant ovarian cancer. For example, Eli Lilly and Company recently received FDA Breakthrough Therapy designation for sofetabart mipitecan, an antibody-drug conjugate targeting folate receptor alpha. The therapy is being evaluated in the Phase III FRAmework-01 trial as a monotherapy in platinum-resistant ovarian cancer and in combination with bevacizumab in platinum-sensitive ovarian cancer.

Merck also reported Phase III results for Keytruda (pembrolizumab) used with paclitaxel, with or without bevacizumab, showing improved overall survival compared with paclitaxel with or without bevacizumab. This regimen is FDA-approved for patients whose tumors express PD-L1.

A Phase II study from ImmunityBio is evaluating an NK cell-based treatment combined with an IL-15-based agent and chemotherapy in patients with recurrent platinum-resistant ovarian cancer. The trial is currently recruiting participants.

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