Trial Outcomes & Findings for Study of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma (NCT NCT03552380)

NCT ID: NCT03552380

Last Updated: 2024-09-03

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

From C1D1 until death or up to 31 months.

Results posted on

2024-09-03

Participant Flow

Participant milestones

Participant milestones
Measure	Phase II, Dose Level 1: Entinostat 5 mg With Nivolumab and Ipilimumab Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2 : Entinostat 3 mg With Nivolumab and Ipilimumab Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Study Treatment STARTED	5	7
Study Treatment COMPLETED	0	1
Study Treatment NOT COMPLETED	5	6
Follow up STARTED	5	7
Follow up COMPLETED	0	0
Follow up NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase II, Dose Level 1: Entinostat 5 mg With Nivolumab and Ipilimumab Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2 : Entinostat 3 mg With Nivolumab and Ipilimumab Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Study Treatment Disease Progression	3	4
Study Treatment Adverse Event	2	2
Follow up PI request to move remaining patients on follow-up to Off study	2	2
Follow up Death	3	4
Follow up Site IRB terminated	0	1

Baseline Characteristics

Study of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase II, Dose Level 1: Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Eastern Cooperative Onology group (ECOG) Performance Status ECOG = 0	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Eastern Cooperative Onology group (ECOG) Performance Status ECOG = 1	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From C1D1 until death or up to 31 months.

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Objective Response Rate (ORR) Via RECIST 1.1	20 percentage of participants Interval 5.1 to 71.6	42.9 percentage of participants Interval 9.9 to 81.6

SECONDARY outcome

Timeframe: From C1D1 until death or up to 31 months

Assess adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Number of Participants With Adverse Events Number of patients had at least one adverse event of any grade.	5 Participants	7 Participants
Number of Participants With Adverse Events Number of patients had at least one grade 3 or greater adverse event.	5 Participants	3 Participants
Number of Participants With Adverse Events Number of patients had at least one grade 3 or greater treatment related adverse event	5 Participants	2 Participants
Number of Participants With Adverse Events Number of patients having serious adverse event.	3 Participants	3 Participants

SECONDARY outcome

Timeframe: From C1D1 until death up to 31 months

Per immune-related response criteria (irRC): Complete Response(irCR), Disappearance of all target and nontarget lesions; Partial Reponse (irPR), ≥ 50% decrease in tumor burden compared with baseline; Progressive Disease (irPD), \>= 25% increase in tumour burden relative to nadir or the appearance new lesions; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD. Overall Response (OR) = irCR + irPR

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Objective Response Rate Via Immune Related Response Criteria (irRC)	20 Percentage of participants Interval 5.1 to 71.6	28.6 Percentage of participants Interval 3.7 to 71.0

SECONDARY outcome

Timeframe: Up to 31 months.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from starting treatment to disease progression met by RECIST 1.1 or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Progression Free Survival (PFS) Via RECIST 1.1	4.3 months Interval 1.3 to Upper limit was not reached due to an insufficient number of participants with events.	11.7 months Interval 1.9 to Upper limit was not reached due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to 31 months

Per immune-related response criteria (irRC): Complete Response(irCR), Disappearance of all target and nontarget lesions; Partial Reponse (irPR), ≥ 50% decrease in tumor burden compared with baseline; Progressive Disease (irPD), \>= 25% increase in tumour burden relative to nadir or the appearance new lesions; Stable Disease (irSD), not meeting criteria for irCR or irPR or irPD. PFS is defined as time from starting treatment to disease progression met by irRC or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Progression Free Survival (PFS) Via irRC	4.3 months Interval 1.3 to Upper limit was not reached due to an insufficient number of participants with events.	11.7 months Interval 5.9 to Upper limit was not reached due to an insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to a maximum of 59 months

OS is defined from Day 1 of treatment until death as a result of any cause

Outcome measures

Outcome measures
Measure	Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab n=5 Participants Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 Participants Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Overall Survival (OS)	49.9 months Interval 6.7 to Upper limit was not reached due to an insufficient number of participants with events.	36 months Interval 5.9 to Upper limit was not reached due to an insufficient number of participants with events.

Adverse Events

Phase II, Dose Level 1: Entinostat 5 mg With Nivolumab and Ipilimumab

Serious events: 3 serious events

Other events: 5 other events

Deaths: 3 deaths

Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab

Serious events: 3 serious events

Other events: 7 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Phase II, Dose Level 1: Entinostat 5 mg With Nivolumab and Ipilimumab n=5 participants at risk Patients received oral entinostat at a dose of 5 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.	Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab n=7 participants at risk Patients received oral entinostat at a dose of 3 mg every 7 days continuously with nivolumab at a dose of 3 mg/kg mg IV every three weeks in combination with ipilimumab at a dose of 1 mg/kg every 3 weeks X 4 doses. Then, nivolumab 480 mg was continued every 4 weeks.
Investigations Platelet count decreased	20.0% 1/5 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Infections and infestations Skin infection	20.0% 1/5 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Gastrointestinal disorders Vomiting	20.0% 1/5 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	0.00% 0/7 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Endocrine disorders Adrenal insufficiency	0.00% 0/5 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	14.3% 1/7 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/5 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	14.3% 1/7 • Number of events 2 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Cardiac disorders Heart failure	0.00% 0/5 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	14.3% 1/7 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/5 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	14.3% 1/7 • Number of events 1 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/5 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.	14.3% 1/7 • Number of events 3 • All-Cause Mortality was monitored up to a maximum of 59 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 31 months. Adverse events were collected for every subject at every cycle of treatment (14 cycles). First 4 cycles at an interval of 21 days and rest at an interval of 28 days from the time of consent until 100 days after last treatment. Serious adverse events were reported from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first.

Other adverse events

Additional Information

Annesha Majumdar

Hoosier Cancer Research Network

Phone: 3179212050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place