Intermittent Relacorilant With Nab-Paclitaxel Extends Survival in Recurrent, Platinum-Resistant Ovarian Cancer

Thomas Herzog, MD

The combination of intermittent relacorilant (CORT-125134) and nab-paclitaxel (Abraxane) achieved a 33% reduction in the risk of death compared with nab-paclitaxel alone in women with recurrent, platinum-resistant ovarian cancer, according to an announcement by Corcept Therapeutics, Inc.¹

The median overall survival (OS) in the intermittent combination arm was 13.9 months (95% CI, 11.1-18.4) compared with 12.2 months (95% CI, 7.7-15.3) with nab-paclitaxel (HR, 0.67; 95% CI, 0.43-1.03; P = .066).

“Corcept has introduced a novel oncologic therapeutic platform, cortisol modulation. These results constitute a potentially important medical advance,” said Thomas Herzog, MD, deputy director at the University of Cincinnati Cancer Center, member of the board of directors of the Gynecologic Oncology Group (GOG) Foundation, and associate director of GOG Partners. “In this large, randomized study, women with recurrent, platinum-resistant ovarian cancer who were administered relacorilant at the time they received nab-paclitaxel exhibited meaningful improvements in progression-free survival [PFS], duration of response [DOR], and overall survival–without increased side effects–compared to women who received nab-paclitaxel alone. For this patient population, relacorilant plus nab-paclitaxel has the potential to become a new standard of care.”

In the phase 2, open-label, multicenter, randomized, 3-arm study (NCT03776812), 178 patients with recurrent, platinum-resistant ovarian cancer were included. The primary end point being assessed in the study was PFS, and secondary end points include objective response rate (ORR), DOR, response according to Gynecological Cancer Intergroup criteria, best overall response rate, PFS rate, PFS in the crossover population, ORR in the crossover population, DOR in the crossover population, best overall response in the crossover population, CA-125 response, OS, and combined response according to RECISTS v1.1.

Patients in the study are assigned 1:1:1 to receive with oral relacorilant 100 mg once daily in combination with nab-paclitaxel 80 mg/m2, oral relacorilant 150 mg combined with nab-paclitaxel 80 mg/m2, both compared with the arm of nab-paclitaxel 100 mg/m2.

Those enrolled in the study were females aged 18 years or older with histologic diagnosis of high grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma. The study excluded those with clear cell, mucinous and borderline histologic subtypes. Patients were required to have received at least 1 line of therapy with evidence of cancer progression within 6 months after the last dose of platinum-based therapy.

Patients must have also had measurable disease by RECIST 1.1, an ECOG performance status of 0 or 1, and adequate organ and bone marrow function. The study is active but no longer recruiting patients.²

“We are excited to receive these survival data, which have continued to improve as the trial has progressed,” said Bill Guyer, PharmD, chief development officer, Corcep, in the press release.1 “If our phase 3 trial replicates the results in progression-free survival, duration of response, and overall survival that we’ve seen in phase 2, it will be an unprecedented success for patients with ovarian cancer. No approved therapy has been shown to significantly extend survival compared to standard chemotherapy in women with platinum-resistant ovarian cancer. We plan to meet with the FDA as soon as possible to define the best path forward and to open our phase 3 trial in the second quarter of 2022.”

_REFERENCES:

_{1. Relacorilant plus nab-paclitaxel extends survival in women with recurrent, platinum-resistant ovarian cancer. News release. Corcept Therapeutics, Inc. March 30, 2022. Accessed April 1, 2022. https://bit.ly/3uKjYDn}

_{2. Study of relacorilant in combination with nab-paclitaxel for patients with recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. Clinicaltrials.gov. Updated June 8, 2021. Accessed April 1, 2022. https://bit.ly/3K2OVce}