Trial Outcomes & Findings for Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma (NCT NCT03562507)

Last Updated: 2024-05-20

Results Overview

The percentage of patients in Cohort B that achieve a complete response (CR) or partial response (PR). Response will be assessed by combined Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immune-related (ir)RECIST.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Up to 24 months after last dose of study treatment

Results posted on

2024-05-20

Participant Flow

Participant milestones

Participant milestones
Measure	ESK981 Monotherapy ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
Overall Study STARTED	8	0
Overall Study COMPLETED	8	0
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Multi-center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Renal Cell Carcinoma

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to 24 months after last dose of study treatment

Population: No patients were enrolled in the ESK984 and Nivolumab combo arm (cohort B)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months after last dose of study treatment, 5 month treatment duration on average, no CR or PR responses were recorded.

The percentage of patients in Cohort A that achieve a complete response (CR) or partial response (PR). Response will be assessed by RECIST v1.1.

Outcome measures

Outcome measures
Measure	ESK981 and Nivolumab (Cohort B) n=8 Participants ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
The Percentage of Patients That Respond to Treatment With ESK981 Monotherapy (Cohort A).	0 Participants	—

SECONDARY outcome

Timeframe: Up to 24 months after last dose of study treatment

Population: No patients were enrolled in the ESK984 and Nivolumab combo arm (cohort B)

Overall survival time measured from start of treatment until up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).

Outcome measures

Outcome measures
Measure	ESK981 and Nivolumab (Cohort B) n=8 Participants ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
Median Overall Survival Time	24.5 Months Interval 14.6 to All the dispersion measures cannot be estimated as we have too few patients. Per PI, there were insufficient number of participants with events to properly measure	—

SECONDARY outcome

Timeframe: Up to 24 months after last dose of study treatment

Population: No patients were enrolled into the combo arm (cohort B)

Measured from start of treatment to time of progression or death, or up to 24 months after the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy). Disease progression will be assessed by RECIST v1.1 in Cohort A and by combined RECIST v1.1/irRECIST in Cohort B.

Outcome measures

Outcome measures
Measure	ESK981 and Nivolumab (Cohort B) n=8 Participants ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
Progression Free Survival Time	1.7 months Interval 1.6 to 8.1	—

SECONDARY outcome

Timeframe: Up to approximately 24 months after treatment start

Population: No patients were enrolled into the combo arm (cohort B)

Measured from the first to the last dose of study treatment in Cohort A (ESK981 monotherapy) and in Cohort B (combination of ESK981 and nivolumab therapy).

Outcome measures

Outcome measures
Measure	ESK981 and Nivolumab (Cohort B) n=8 Participants ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
Duration of Therapy	2.1 Months Interval 0.6 to 19.4	—

SECONDARY outcome

Timeframe: Up to 24 months after last dose of study treatment

Population: There were no responses to therapy

Measured from the time of complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Response will be assessed by RECIST v1.1 (Cohort A) and by combined RECIST v1.1/irRECIST (Cohort B).

Outcome measures

Outcome data not reported

Adverse Events

ESK981 Monotherapy (Cohort A)

Serious events: 2 serious events

Other events: 8 other events

Deaths: 3 deaths

ESK981 and Nivolumab (Cohort B)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ESK981 Monotherapy (Cohort A) n=8 participants at risk ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles	ESK981 and Nivolumab (Cohort B) ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle
Gastrointestinal disorders Abdominal pain	12.5% 1/8 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B	— 0/0 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B
Musculoskeletal and connective tissue disorders Back Pain	12.5% 1/8 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B	— 0/0 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B
Infections and infestations Lung Infection	12.5% 1/8 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B	— 0/0 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B	— 0/0 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B	— 0/0 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 60 days after the last dose of study drug treatment. Data as collected for 2.5 years No subjects were enrolled in Cohort B

Other adverse events

Additional Information

ClinicalTrials.gov Cancer Center Admin

University of Michigan Rogel Cancer Center

Phone: 734-936-9499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ESK981 Monotherapy n=8 Participants ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles	ESK981 and Nivolumab ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle ESK981: ESK981: 160 mg (4 capsules) PO daily for 5 consecutive days followed by a 2-day off drug in each week, repeated weekly in 4-week (28-day) cycles Nivolumab: 480 mg/dose IV, Day 1 of each 28-day cycle	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	—	4 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	—	4 Participants n=5 Participants
Age, Continuous	66 years n=5 Participants	—	66 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	—	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	—	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	—	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	—	8 participants n=5 Participants