Solid Tumors
Conditions
Keywords
CORT125134, nab-paclitaxel, Triple-Negative Breast Cancer, Ovarian Epithelial Cancer, GR Antagonist, Glucocorticoid Receptor Antagonist, Pancreatic Cancer, Solid Tumors, Relacorilant, Abraxane
Brief summary
The purpose of this study was to assess the safety of the combination of relacorilant (CORT125134), a novel glucocorticoid receptor (GR) antagonist, and nab- paclitaxel in participants with solid tumors and to determine the preliminary efficacy of the combination of relacorilant and nab-paclitaxel. The structure for the study was a single arm, non-randomized, open- label, multicenter trial with no control group.
Detailed description
The study consisted of two segments to evaluate alternative dosing schedules of relacorilant administered at escalating dose levels. Segment I was to evaluate a continuous-dosing regimen and Segment II was to evaluate an intermittent-dosing regimen. Enrollment in Segment I and Segment II were mutually exclusive, and the two segments enrolled participants concurrently. In Segment I continuous-dosing cohorts, participants received a single nab-paclitaxel lead-in infusion on Day 1 of Week -2 before Cycle 1, and oral relacorilant lead-in once-daily of Week -1 before Cycle 1. After the Data Review Committee review of data for 2 dose levels, the nab-paclitaxel lead-in was discontinued. The lead-in period was followed by oral relacorilant administered continuously once daily, in combination with nab-paclitaxel infusions on Days 1, 8, and 15 of each 28-day cycle. Segment 1 enrolled a total of 64 participants. In Segment II intermittent-dosing cohorts, participants received a single relacorilant lead-in dose on Day -1 before Cycle 1, followed by oral relacorilant, administered intermittently the day before, the day of, and the day after nab-paclitaxel infusions on Days 1, 8, and 15 of each 28-day cycle. Segment II enrolled a total of 21 participants.
Interventions
DRUGRelacorilant with nab-paclitaxel
Relacorilant is supplied as capsules for oral dosing. Nab-paclitaxel administered as an IV infusion.
Sponsors
Corcept Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with advanced or metastatic solid tumors who have disease progression after treatment with available therapies and for whom nab-paclitaxel treatment is appropriate. * Measurable or evaluable disease. * Up to 3 prior cytotoxic chemotherapeutics regimens or myelosuppressive therapies in the advanced setting. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * For Part 2 Only: Platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer, or Triple Negative Breast Cancer with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in at least 1 lesion, that in the opinion of the Investigator is appropriate to treat with nab-paclitaxel.
Exclusion criteria
* Any major surgery within 4 weeks prior to the first dose of study drug. * Some protocol specified treatments prior to the first dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicity | Up to completion of Cycle 1 (up to 28 days) | The Maximum Tolerated Dose and the development regimen of relacorilant with nab-paclitaxel was determined by the number of participants with dose-limiting toxicities as defined in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | Up to 28 days after the last dose of study drug (Segment I: up to approximately 2.5 years, Segment II: up to approximately 1.5 years) | Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From the time of response up to the last disease assessment (up to 512 days) | Duration of response (DOR) is defined as the date that criteria are met for CR or PR until the first date that progressive disease or death is objectively documented, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment |
| Progression-free Survival | Up to 512 days | Progression-free survival is defined as the time from date of first dose of relacorilant or nab-paclitaxel, whichever is earliest, to the date of documented disease progression per RECIST v1.1 or death for any cause, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment. |
| Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Up to 512 days | Best response is defined by RECIST v1.1 as the best response recorded from the date of the first dose of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses). |
| Overall Survival | Up to 512 days | Overall survival is defined as the time from date of the first dose of relacorilant or nab paclitaxel, whichever is earliest, to the date of death for any cause. Participants with no documentation of death on-study are censored at the date at which they are last known to be alive. |
| Objective Response Rate | Up to 512 days | Objective response rate is defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as best response of complete response (CR) or partial response (PR) from the start of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses). |
| Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1 | — |
| Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1 | — |
| Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1 | — |
| Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1 | — |
| Clinical Benefit Rate | Up to 512 days | Clinical benefit rate is defined as the participants who have achieved CR or PR (including both confirmed and unconfirmed responses), or stable disease for 16 weeks or greater. |
Countries
United States
Participant flow
Pre-assignment details
The starting population included all study participants.
Participants by arm
| Arm | Count |
|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen Following lead-in, participants received relacorilant 100 mg, administered orally once daily, in combination with nab-paclitaxel 60 mg/m\^2 infusions on Days 1, 8, and 15 of each 28-day cycle. | 14 |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen Following lead-in, participants received relacorilant 100 mg, administered orally once daily, in combination with nab-paclitaxel 80 mg/m\^2 infusions on Days 1, 8, and 15 of each 28-day cycle. | 34 |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen Following lead-in, participants received relacorilant 150 mg, administered orally once daily, in combination with nab-paclitaxel 80 mg/m\^2 infusions on Days 1, 8, and 15 of each 28-day cycle. | 6 |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen Following lead-in, participants received relacorilant 150 mg, administered orally the day before, the day of, and the day after nab-paclitaxel 80 mg/m\^2 infusions on Days 1, 8, and 15 of each 28-day cycle. | 14 |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen Following lead-in, participants received relacorilant 200 mg, administered orally the day before, the day of, and the day after nab-paclitaxel 100 mg/m\^2 infusions on Days 1, 8, and 15 of each 28-day cycle. | 5 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 1 | 1 | 3 |
| Overall Study | Disease progression | 11 | 23 | 4 | 10 | 1 |
| Overall Study | Enrolled not treated | 1 | 5 | 0 | 2 | 0 |
| Overall Study | Missing | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 2 | 3 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 5 | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 57.0 years STANDARD_DEVIATION 10.6 | 60.6 years STANDARD_DEVIATION 12.81 | 56.8 years STANDARD_DEVIATION 18.51 | 59.6 years STANDARD_DEVIATION 12.02 | 64.8 years STANDARD_DEVIATION 10.21 | 59.7 years STANDARD_DEVIATION 12.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 31 Participants | 4 Participants | 12 Participants | 5 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 12 Participants | 31 Participants | 4 Participants | 9 Participants | 2 Participants | 58 Participants |
| Region of Enrollment United States | 14 participants | 34 participants | 6 participants | 14 participants | 5 participants | 73 participants |
| Sex: Female, Male Female | 9 Participants | 20 Participants | 4 Participants | 14 Participants | 3 Participants | 50 Participants |
| Sex: Female, Male Male | 5 Participants | 14 Participants | 2 Participants | 0 Participants | 2 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 12 / 14 | 19 / 34 | 5 / 6 | 4 / 14 | 4 / 5 |
| other Total, other adverse events | 13 / 14 | 31 / 34 | 6 / 6 | 14 / 14 | 5 / 5 |
| serious Total, serious adverse events | 6 / 14 | 18 / 34 | 5 / 6 | 8 / 14 | 3 / 5 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicity
The Maximum Tolerated Dose and the development regimen of relacorilant with nab-paclitaxel was determined by the number of participants with dose-limiting toxicities as defined in the protocol.
Time frame: Up to completion of Cycle 1 (up to 28 days)
Population: The dose-limiting toxicity evaluable population was participants who completed 1 cycle of treatment and assessment or received at least 1 dose of relacorilant and discontinued treatment before completing Cycle 1 due to toxicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Number of Participants With Dose-limiting Toxicity | 0 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Number of Participants With Dose-limiting Toxicity | 8 Participants |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Number of Participants With Dose-limiting Toxicity | 2 Participants |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Number of Participants With Dose-limiting Toxicity | 2 Participants |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Number of Participants With Dose-limiting Toxicity | 3 Participants |
Secondary
Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: Up to 28 days after the last dose of study drug (Segment I: up to approximately 2.5 years, Segment II: up to approximately 1.5 years)
Population: The safety population was all enrolled participants who received at least 1 dose of relacorilant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | 13 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | 24 Participants |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | 5 Participants |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | 13 Participants |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Number of Participants With One or More Adverse Events Related to Treatment With Relacorilant | 5 Participants |
Other Pre-specified
Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level
Best response is defined by RECIST v1.1 as the best response recorded from the date of the first dose of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses).
Time frame: Up to 512 days
Population: The population was all enrolled participants who received at least 1 dose of relacorilant and had tumor biopsy tissue assessed for GR. These data were planned to be summarized by GR H-score category: above or below the overall median value.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Partial response | 3 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Progressive disease | 4 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Stable disease | 7 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Missing or not evaluable | 1 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Complete response | 1 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Missing or not evaluable | 4 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Complete response | 0 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Partial response | 1 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Stable disease | 7 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Best Response Rate in Participants With Tumor Glucocorticoid Receptor (GR) Above or Below the Median Overall Level | Progressive disease | 4 Participants |
Other Pre-specified
Clinical Benefit Rate
Clinical benefit rate is defined as the participants who have achieved CR or PR (including both confirmed and unconfirmed responses), or stable disease for 16 weeks or greater.
Time frame: Up to 512 days
Population: All enrolled participants who received at least 1 dose of relacorilant. The Statistical Plan specified summarization of Clinical Benefit Rate results by Segment I and Segment II.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Clinical Benefit Rate | 13 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Clinical Benefit Rate | 6 Participants |
Other Pre-specified
Duration of Response
Duration of response (DOR) is defined as the date that criteria are met for CR or PR until the first date that progressive disease or death is objectively documented, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment
Time frame: From the time of response up to the last disease assessment (up to 512 days)
Population: All enrolled participants who received at least 1 dose of relacorilant. This outcome measure assessed participants with confirmed responses to treatment. The Statistical Plan specified summarization of Duration of Response results by Segment I and Segment II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Duration of Response | 9.7 months |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Duration of Response | NA months |
Other Pre-specified
Objective Response Rate
Objective response rate is defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as best response of complete response (CR) or partial response (PR) from the start of relacorilant or nab-paclitaxel, whichever is earliest, across all time points during study observation period (including both confirmed and unconfirmed responses).
Time frame: Up to 512 days
Population: All enrolled participants who received at least 1 dose of relacorilant. The Statistical Plan specified summarization of Objective Response Rate results by Segment I and Segment II.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Objective Response Rate | 7 Participants |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Objective Response Rate | 2 Participants |
Other Pre-specified
Overall Survival
Overall survival is defined as the time from date of the first dose of relacorilant or nab paclitaxel, whichever is earliest, to the date of death for any cause. Participants with no documentation of death on-study are censored at the date at which they are last known to be alive.
Time frame: Up to 512 days
Population: All enrolled participants who received at least 1 dose of relacorilant. The Statistical Plan specified summarization of Overall Survival results by Segment I and Segment II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Overall Survival | 8.3 Months |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Overall Survival | 16.5 Months |
Other Pre-specified
Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant
Time frame: Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Population: The population analyzed was participants in the Safety Population with adequate pharmacokinetic data. One participant in the Segment II: relacorilant 150 mg + nab-paclitaxel 80 mg/m\^2 intermittent dosing group had insufficient data to evaluate AUC0-24 for relacorilant.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | 3380 ng*h/mL | Geometric Coefficient of Variation 139 |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | 3780 ng*h/mL | Geometric Coefficient of Variation 110 |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | 7480 ng*h/mL | Geometric Coefficient of Variation 50 |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | 3300 ng*h/mL | Geometric Coefficient of Variation 104 |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Area Under the Concentration-time Curve From Zero to 24 Hours (AUC0-24) of Plasma Relacorilant | 7440 ng*h/mL | Geometric Coefficient of Variation 146 |
Other Pre-specified
Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel
Time frame: Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Population: The population analyzed was participants in the Safety Population with adequate pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | 2290 ng*h/mL | Geometric Coefficient of Variation 48.5 |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | 3580 ng*h/mL | Geometric Coefficient of Variation 67.5 |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | 3380 ng*h/mL | Geometric Coefficient of Variation 12.7 |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | 3440 ng*h/mL | Geometric Coefficient of Variation 62.8 |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: AUC0-24 of Plasma Nab-Paclitaxel | 5910 ng*h/mL | Geometric Coefficient of Variation 73.7 |
Other Pre-specified
Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel
Time frame: Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Population: The population analyzed was participants in the Safety Population with adequate pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | 1810 ng/mL | Geometric Coefficient of Variation 71 |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | 2660 ng/mL | Geometric Coefficient of Variation 69.9 |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | 1560 ng/mL | Geometric Coefficient of Variation 79.3 |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | 2600 ng/mL | Geometric Coefficient of Variation 70 |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Cmax of Plasma Nab-Paclitaxel | 3070 ng/mL | Geometric Coefficient of Variation 41.5 |
Other Pre-specified
Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant
Time frame: Segment I: before dosing and up to 24 hours after dosing on Cycle 1 Day 8; Segment II: before dosing and up to 24 hours after dosing on Cycle 1 Day 1
Population: The population analyzed was participants in the Safety Population with adequate pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | 363 ng/mL | Geometric Coefficient of Variation 100 |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | 423 ng/mL | Geometric Coefficient of Variation 88.8 |
| Segment I: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | 767 ng/mL | Geometric Coefficient of Variation 47.4 |
| Segment II: Relacorilant 150 mg + Nab-paclitaxel 80 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | 546 ng/mL | Geometric Coefficient of Variation 89.4 |
| Segment II: Relacorilant 200 mg + Nab-paclitaxel 100 mg/m^2 Intermittent Dosing Regimen | Pharmacokinetics: Maximum Concentration (Cmax) of Plasma Relacorilant | 897 ng/mL | Geometric Coefficient of Variation 55.2 |
Other Pre-specified
Progression-free Survival
Progression-free survival is defined as the time from date of first dose of relacorilant or nab-paclitaxel, whichever is earliest, to the date of documented disease progression per RECIST v1.1 or death for any cause, whichever occurs first. Participants with no documentation of disease progression or death on-study are censored at the date of last available tumor assessment.
Time frame: Up to 512 days
Population: All enrolled participants who received at least 1 dose of relacorilant. The Statistical Plan specified summarization of Progression-free Survival results by Segment I and Segment II.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 60 mg/m^2 Continuous Dosing Regimen | Progression-free Survival | 2.8 Months |
| Segment I: Relacorilant 100 mg + Nab-paclitaxel 80 mg/m^2 Continuous Dosing Regimen | Progression-free Survival | 3.7 Months |