Relacorilant

Relacorilant is used in combination with nab-paclitaxel. Refer to the Prescribing Information of nab-paclitaxel for pregnancy information.

Based on findings in animals, relacorilant can cause fetal harm when administered to a pregnant woman. There are no available data on relacorilant use in pregnant women to inform drug-associated risk. In animal embryo-fetal development studies, oral administration of relacorilant to pregnant rabbits during the period of organogenesis resulted in embryo-fetal mortality and structural abnormalities at maternal doses of ≥10 mg/kg/day (0.6 times the human exposure based on area under the curve (AUC) at the recommended dose). Oral administration of relacorilant to pregnant rats during the period of organogenesis did not result in fetal malformations.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is between 2 to 4% and 15 to 20%, respectively.

Relacorilant is used in combination with nab-paclitaxel. Refer to the Prescribing Information of nab-paclitaxel for lactation information.

There are no data on the presence of relacorilant or its metabolites in animal or human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with relacorilant and for one week after the last dose.

Carcinogenesis

In a 6-month carcinogenicity study, transgenic rasH2 mice were orally administered up to 100 mg/kg/day relacorilant. In a 2-year carcinogenicity study, rats were orally administered up to 10 mg/kg/day in male rats (1.3 times the human exposure based on AUC at the recommended dose) and 3 mg/kg/day in female rats (0.7 times the human exposure based on AUC at the recommended dose). There was no evidence of relacorilant-induced carcinogenicity in either study.

Mutagenesis

Relacorilant was not genotoxic in the bacterial reverse mutation (Ames) assay, an in vitro human lymphocyte micronucleus assay, or an in vivo micronucleus assay in rats.

Impairment of Fertility

In a fertility study, relacorilant was administered orally to male rats prior to and throughout mating and to female rats prior to mating and up to the implantation day (gestation day 7). Relacorilant had no effect on fertility or reproductive function in male or female rats at doses up to 40 mg/kg/day (≥4.5 times the human exposure based on AUC at the recommended dose).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of relacorilant in combination with nab-paclitaxel was evaluated in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in ROSELLA.

Patients received relacorilant (150 mg orally on the day before, the day of, and the day after each administration of nab-paclitaxel 80 mg/m² intravenous infusion on Days 1, 8 and 15 of each 28-day cycle (n=188) or nab-paclitaxel 100 mg/m² intravenous infusion (n=190) until disease progression or unacceptable toxicity. Relacorilant dosing was interrupted whenever nab-paclitaxel was interrupted. The median duration of relacorilant treatment was 4.7 months (range: 0.2 to 24).

Serious adverse reactions occurred in 35% of patients who received relacorilant in combination with nab-paclitaxel. Serious adverse reactions in ≥2% of patients were neutropenia (4%), pneumonia (3.2%), pleural effusion (3.2%), febrile neutropenia (2.1%), and fatigue (2.1%). Fatal adverse reactions occurred in 2.1% of patients who received relacorilant in combination with nab-paclitaxel including septic shock (0.5%), cardiac arrest (0.5%), ischemic stroke (0.5%), and intestinal perforation (0.5%).

Permanent discontinuation of relacorilant in combination with nab-paclitaxel due to adverse reactions occurred in 9% of patients. The adverse reaction which resulted in permanent discontinuation of relacorilant in >2% of patients was intestinal obstruction (2.6%).

Dosage interruptions of relacorilant due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruptions of relacorilant in combination with nab-paclitaxel in ≥5% of patients included neutropenia (44%), anemia (12%), and fatigue (7%).

Dose reductions of relacorilant due to an adverse reaction occurred in 7.4% of patients and dose reductions of nab-paclitaxel occurred in 48% of patients. Adverse reactions which required dose reductions of relacorilant included fatigue (1.6%), decreased appetite (1.2%), abdominal pain (0.5%), neutropenia (0.5%), edema (0.5%), and sciatica (0.5%).

The most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, fatigue, nausea, diarrhea, decreased platelets, rash, and decreased appetite.

Table 1 and 2 summarize adverse reactions and laboratory abnormalities, respectively, occurring in ≥10% of patients who received relacorilant in combination with nab-paclitaxel in ROSELLA.

Table 1. Adverse Reactions Occurring in ≥10% of Patients Who Received Relacorilant in Combination with Nab-Paclitaxel in ROSELLA:

^a Includes multiple related terms

Clinically relevant adverse reactions occurring in <10% of patients who received relacorilant in combination with nab-paclitaxel in ROSELLA included dry eye (8.5%), hypotension (8.5%), hypertension (4.8%), acute kidney injury (4.3%), febrile neutropenia (3.7%), and syncope (2.7%).

Table 2. Select Laboratory Abnormalities ≥10% for All Grades, in Patients Who Received Relacorilant in Combination with Nab-Paclitaxel in ROSELLA: