Relacorilant Plus Nab-Paclitaxel Improved Survival, Response in Platinum-Resistant Ovarian Cancer

According to results of a phase 2 trial, intermittent relacorilant, an investigational, orally administered, selective glucocorticoid receptor modulator, plus nab-paclitaxel showed improved progression-free survival (PFS), duration of response (DOR), and overall-survival (OS) compared to nab-paclitaxel monotherapy among pre-treated patients with recurrent, platinum-resistant/refractory high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma. 

“Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor,” wrote Nicoletta Colombo, MD, European Institute of Oncology, IRCCS, Milan, Italy, and coauthors. According to preclinical evidence, “selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.”

In this 3-arm, controlled, open-label study, 178 patients previously treated with ≤4 prior lines of chemotherapeutic regimens were randomized on a 1-to-1-to-1 basis to receive 80 mg/m2 of nab-paclitaxel plus 150 mg of intermittent relacorilant administered before and after nab-paclitaxel (n = 60, intermittent arm), nab-paclitaxel plus 100 mg of continuous relacorilant (n = 58, continuous arm), or 100 mg/m2 of nab-paclitaxel monotherapy administered on days 1, 8, and 15 of each cycle (n = 60, nab-paclitaxel monotherapy arm). The primary end point was PFS based on investigator assessment. Secondary end points included objective response rate (ORR), DOR, OS, and safety. 

At a median-follow up of 11.1 months, results indicated intermittent relacorilant plus nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038) and DOR (HR, 0.36; P = .006), with similar ORR compared to that of nab-paclitaxel monotherapy across all arms. Additionally, at a median follow-up of 22.5 months, pre-planned OS analysis indicated that the OS HR was 0.67 (P = .066) for intermittent relacorilant plus nab-paclitaxel. Despite showing numerical improvement, upon calculation of Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). 

The most common grade ≥ 3 adverse events included neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia. Across all study arms, adverse events were comparable. There were 14 serious adverse events determined to be related to one or both study drugs: anemia, pneumocystis jirovecci pneumonia, and general deteriorationg of physical health in the intermittent arm, white blood cell decreased, anemia, abdominal pain, back pain, constipation and melanocytic hyperplasia in the contiuous arm, and upper respiratory tract infection, hypocalcemia, hypomagnesemia, hypophosphatemia, and syncope in the nab-paclitaxel monotherapy arm.

According to Dr Colombo and coauthors, “these findings highlight the potential of [glucocorticoid receptor] modulation as a novel mechanism to restore chemosensitivity and enhance chemotherapy efficacy.” 

“Recurrent platinum resistant ovarian cancer is a significant clinical issue. This randomized phase [2] trial of relacorilant [plus] nab-paclitaxel provides promising data that paved the way for a confirmatory ongoing phase [3] trial,” added deputy editor for Journal of Clinical Oncology Bruce G. Haffty, MD, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 

Source: 
Colombo N, Van Gorp T, Matulonis UA, et al. Relacorilant + nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer: A three-arm, randomized, controlled, open-label phase II study. J Clin Oncol. Published online June 26, 2023. doi:10.1200/JCO.22.02624