Relacorilant Plus Nab-Paclitaxel Demonstrates Preliminary Efficacy in Metastatic Pancreatic Cancer

Relacorilant (CORT125134), a non-steroidal, selective modulator of the glucocorticoid receptor, administered in combination with nab-paclitaxel elicited responses in patients with metastatic pancreatic cancer, leading to the halting of enrollment in the phase 2 RELIANT trial (NCT04329949), according to a press release from Corcept Therapeutics, Inc.¹

“RELIANT evaluated relacorilant plus nab-paclitaxel in pancreatic cancer patients who had relapsed following at least 2 prior lines of therapy, including treatment with nab-paclitaxel in almost all cases,” said Andreas Grauer, MD, chief medical officer, Corcept Therapeutics. “Two of 31 evaluable patients exhibited tumor shrinkage designated as a partial response, a response rate of 6 percent, while 15 patients achieved stable disease for at least 12 weeks. The combination was well-tolerated. These data are similar to those of our phase 1 study.”

RELIANT is a single-arm, multicenter, open-label, phase 3 study of 80 patients with metastatic pancreatic cancer being treated with the investigational combination. For the interim analysis, 40 patients were enrolled and administered 199 mg of relacorilant daily with 80 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of every 28-day cycle. The primary end point explored was the objective response rate (ORR) per Blinded Independent Central Review. RELIANT also evaluated ORR by investigator assessment, best overall response, duration of response, disease control rate, progression-free survival, overall survival, tumor response per European Organisation for Research Treatment of Cancer criteria, and time to progression.

Relacorilant has been used to treat many oncologic diseases including ovarian cancer and castration-resistant prostate cancer. Outside of cancer, the drug is used mainly to treat Cushing syndrome In a first-in-human study published in Clinical Pharmacology and Drug Development,² it was discovered that the agent was well-tolerated in single doses up to 500 mg as well as repeated doses up to 250 mg once daily for 14 days. The pharmacological activity of relacorilant was also confirmed in this study after it was administered to patients at the 500 mg and 250 mg doses.

A total of 81 subjects were included in the study and given either relacorilant or placebo. The group assessed was a mean age of 39.73 years (range 21-60 years), and had a mean body mass index of 25.75 kg/m2 (range,18.2-30.3 kg/m2). The patients were predominantly male (93.3%) and just 6.7% were female. The patient population was also predominantly White (85.9%), but also included Black, (6.5%), Asian (4.8%), and other (2.8%).

Overall, 46 of the patients enrolled received up to 14 days of treatment with relacorilant or placebo in the study. Safety was assessed after 9 patients discontinued treatment. The most common treatment-emergent adverse event (TEAE) observed was headache. Events of nausea, vomiting, and thirst were also reported by more than 1 patient after they were dosed with the investigational agent. Most TEAEs were considered to be mild and 3 were moderate including nausea in 2 patients and vomiting in 1 patient. The moderate events were considered to be drug-related.

Following multiple doses of relacorilant the overall incidence of TEAEs were still low and were similar to that observed after a single dose. The most common types of TEAEs reported after multiple doses included musculoskeletal and connective tissue disorders, gastrointestinal system disorders, general disorders, and application site conditions. The majority of these TEAEs were mild with the exception of moderate constipation and abdominal pain. In addition, one severe case of back pain was observed.

Based on the preliminary efficacy and know safety of relacorilant, the company plan to initiate a pivotal phase 3 trial in the first quarter of 2022.¹

“Metastatic pancreatic cancer is a dire disease and patients who have relapsed following multiple lines of therapy have no effective treatment options. While our interim analysis suggests that the combination of relacorilant and nab-paclitaxel is active in these patients, the apparent level of benefit does not justify its further study as a treatment for end-stage pancreatic cancer,” said Grauer, in the press release.

_References:

_{1. Preliminary results from RELIANT Trial of relacorilant plus nab-paclitaxel in patients with metastatic pancreatic cancer. New release. Corcept Therapeutics, Inc. June 22, 2021. Accessed June 24, 2021.}

_{2. Assessment of Safety, tolerability, pharmacokinetics, and pharmacological effect of orally administered CORT125134: an adaptive, double-blind, randomized, placebo-controlled phase 1 clinical study. Clin Pharmacol Drug Dev. 2018; 7(4):408-421. doi: 10.1002/cpdd.389. https://bit.ly/3j8fulR}