Trial Outcomes & Findings for Reversing Therapy Resistance With Epigenetic-Immune Modification (NCT NCT02395627)
NCT ID: NCT02395627
Last Updated: 2020-07-07
Results Overview
Objective response rate (ORR) will be defined as the proportion of participants whose status is stable disease (SD) or better (complete response (CR), partial response (PR)) at 24 weeks' follow-up as measured by Response Evaluation Criteria in Solid Tumors (RECIST). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
38 participants
Primary outcome timeframe
Up to 24 weeks
Results posted on
2020-07-07
Participant Flow
Participant milestones
| Measure |
Pembrolizumab Cycle 1 (Group A)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
Tamoxifen
Vorinostat
Pembrolizumab
|
Pembrolizumab Cycle 2 (Group B)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
Tamoxifen
Vorinostat
Pembrolizumab
|
Pembrolizumab Cycle 1 (Group C)
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
Vorinostat
Pembrolizumab
|
|---|---|---|---|
|
Overall Study
STARTED
|
18
|
16
|
4
|
|
Overall Study
COMPLETED
|
15
|
13
|
4
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
0
|
Reasons for withdrawal
| Measure |
Pembrolizumab Cycle 1 (Group A)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
Tamoxifen
Vorinostat
Pembrolizumab
|
Pembrolizumab Cycle 2 (Group B)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
Tamoxifen
Vorinostat
Pembrolizumab
|
Pembrolizumab Cycle 1 (Group C)
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
Vorinostat
Pembrolizumab
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
0
|
|
Overall Study
Did not receive pembrolizumab
|
3
|
1
|
0
|
Baseline Characteristics
Reversing Therapy Resistance With Epigenetic-Immune Modification
Baseline characteristics by cohort
| Measure |
Pembrolizumab Group A
n=18 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab Group B
n=16 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 Participants
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
30-39 years old
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Age, Customized
40-49 years old
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Age, Customized
50-59 years old
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Customized
60-69 years old
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Customized
70-79 years old
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Age, Customized
80-89 years old
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
16 participants
n=7 Participants
|
4 participants
n=5 Participants
|
38 participants
n=4 Participants
|
|
Estrogen Receptor (ER) Type
ER Positive (ER+)
|
18 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Estrogen Receptor (ER) Type
ER Negative (ER-)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: Participants in Group C were off treatment prior to assessment and not included in this analysis
Objective response rate (ORR) will be defined as the proportion of participants whose status is stable disease (SD) or better (complete response (CR), partial response (PR)) at 24 weeks' follow-up as measured by Response Evaluation Criteria in Solid Tumors (RECIST). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Objective Response Rate (ORR)
|
6.67 percentage of participants
|
0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: Up to 1 year post treatment, approximately 24 monthsEach patient who received at least 1 dose of any of the study drugs will be assessed periodically for the development of any grade 3 and higher treatment-related toxicity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4. The investigators will also pay particular attention to pembrolizumab adverse events of clinical interest (ECI), which will predominantly be of immune origin.
Outcome measures
| Measure |
Pembrolizumab Group A
n=18 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=16 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 Participants
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Number of Participants With Treatment-related Adverse Events (AE)
Anorexia
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Adverse Events (AE)
Fatigue
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Adverse Events (AE)
Thrombocytopenia
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-related Adverse Events (AE)
Elevated Transaminitis (Liver Enzymes)
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Adverse Events (AE)
Hyponatremia
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Adverse Events (AE)
Stroke
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 24 monthsPopulation: No participants from Group C achieved an objective response
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Duration of Response
|
17.0 months
Interval 6.5 to 21.7
|
8.8 months
Interval 8.7 to 8.8
|
—
|
SECONDARY outcome
Timeframe: Up to 36 monthsPopulation: No participants from Group C achieved an objective response
Progression-free survival (PFS) is defined as the length of time during and after the treatment that the participant has achieved an objective response, but does not progress as measured by RECIST v.1.1
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Progression Free Survival
|
2.57 months
Interval 1.1 to 21.7
|
2.63 months
Interval 1.0 to 8.6
|
—
|
SECONDARY outcome
Timeframe: Up to 36 monthsOS is defined as the length of time from the start of treatment for participants until death or the study has ended, whichever comes first.
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 Participants
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Overall Survival (OS)
|
14.3 months
Interval 1.0 to 34.8
|
15.0 months
Interval 3.3 to 34.8
|
7.8 months
Interval 3.8 to 29.5
|
SECONDARY outcome
Timeframe: Up to 24 monthsIn the irRC, an immune-related Complete Response (irCR) is defined as the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is defined as a 50% drop in tumour burden from baseline, and immune-related Progressive Disease (irPD) is a 25% increase in tumour burden from the lowest level recorded. All other responses are considered immune-related Stable Disease (irSD). The number of participants with a tumor response of either irCR or irPR will be reported.
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 Participants
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Number of Participants With Tumor Responses Calculated by Immune Related Response-Criteria (irRC)
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 18 weeks, at Cycle 6Population: All necessary data required for inclusion in this analysis could not be obtained for participants in Group C
PD-L1 protein expression on tumor tissue from pre-treatment and post-Cycle-3 biopsies, and any other tumor biospecimens obtained, were evaluated immunohistochemically. Patients were categorized based on detectable PD-L1 expression as Positive or Negative for expression. Participants with positive PD-L1 expression were then reviewed to determine if a clinical benefit was obtained at cycle 6. Clinical benefit was defined as a complete response or partial response per RECIST 1.1.
Outcome measures
| Measure |
Pembrolizumab Group A
n=15 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group A Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab: Group B
n=13 Participants
Estrogen Receptor Positive (ER+) participants
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1)
Group B Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
Estrogen Receptor Negative (ER-) participants
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Number of Participants With a Clinical Response (Clinical Benefit) Based on PD-L1 Expression to Epigenetic Immune Priming
PD-L1 Negative
|
14 Participants
|
12 Participants
|
—
|
|
Number of Participants With a Clinical Response (Clinical Benefit) Based on PD-L1 Expression to Epigenetic Immune Priming
PD-L1 Positive
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With a Clinical Response (Clinical Benefit) Based on PD-L1 Expression to Epigenetic Immune Priming
PD-L1 Positive with clinical benefit at cycle 6
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
Pembrolizumab Group A
Serious events: 6 serious events
Other events: 17 other events
Deaths: 1 deaths
Pembrolizumab Group B
Serious events: 4 serious events
Other events: 15 other events
Deaths: 0 deaths
Pembrolizumab Group C
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pembrolizumab Group A
n=18 participants at risk
Estrogen Receptor Positive participants (ER+)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Group A: Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab Group B
n=16 participants at risk
Estrogen Receptor Positive participants (ER+)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Group B: Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 participants at risk
Estrogen Receptor Negative participants (ER-)
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Nervous system disorders
Dysarthria
|
5.6%
1/18 • Number of events 2 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/18 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Nervous system disorders
Intracranial hemorrhage
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/18 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Vascular disorders
Hematoma
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/18 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/18 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Weight Loss
|
0.00%
0/18 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Renal and urinary disorders
Acute renal failure (ARF)
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
Other adverse events
| Measure |
Pembrolizumab Group A
n=18 participants at risk
Estrogen Receptor Positive participants (ER+)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Group A: Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
Pembrolizumab Group B
n=16 participants at risk
Estrogen Receptor Positive participants (ER+)
Tamoxifen: 20 mg daily orally (starting at Cycle 1) Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Group B: Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 2)
|
Pembrolizumab Group C
n=4 participants at risk
Estrogen Receptor Negative participants (ER-)
Vorinostat: 400 mg 5 days every 7 orally (starting at Cycle 1) Pembrolizumab: 200 mg every 3 weeks intravenously (starting at Cycle 1)
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
6/18 • Number of events 16 • Up to 24 months
|
25.0%
4/16 • Number of events 4 • Up to 24 months
|
50.0%
2/4 • Number of events 2 • Up to 24 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
6/18 • Number of events 8 • Up to 24 months
|
25.0%
4/16 • Number of events 10 • Up to 24 months
|
50.0%
2/4 • Number of events 2 • Up to 24 months
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
6/18 • Number of events 6 • Up to 24 months
|
18.8%
3/16 • Number of events 4 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Constipation
|
33.3%
6/18 • Number of events 6 • Up to 24 months
|
25.0%
4/16 • Number of events 5 • Up to 24 months
|
50.0%
2/4 • Number of events 2 • Up to 24 months
|
|
Gastrointestinal disorders
Dry mouth
|
22.2%
4/18 • Number of events 4 • Up to 24 months
|
12.5%
2/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Abdominal pain
|
22.2%
4/18 • Number of events 4 • Up to 24 months
|
12.5%
2/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Gastritis
|
5.6%
1/18 • Number of events 2 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
General disorders
Fatigue
|
61.1%
11/18 • Number of events 20 • Up to 24 months
|
31.2%
5/16 • Number of events 7 • Up to 24 months
|
100.0%
4/4 • Number of events 8 • Up to 24 months
|
|
General disorders
Pain
|
22.2%
4/18 • Number of events 6 • Up to 24 months
|
12.5%
2/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Metabolism and nutrition disorders
Anorexia
|
27.8%
5/18 • Number of events 10 • Up to 24 months
|
37.5%
6/16 • Number of events 6 • Up to 24 months
|
100.0%
4/4 • Number of events 5 • Up to 24 months
|
|
Investigations
Platelet count decreased
|
22.2%
4/18 • Number of events 7 • Up to 24 months
|
18.8%
3/16 • Number of events 9 • Up to 24 months
|
25.0%
1/4 • Number of events 4 • Up to 24 months
|
|
Investigations
Weight loss
|
16.7%
3/18 • Number of events 4 • Up to 24 months
|
25.0%
4/16 • Number of events 6 • Up to 24 months
|
50.0%
2/4 • Number of events 3 • Up to 24 months
|
|
Investigations
Creatinine increased
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
25.0%
4/16 • Number of events 8 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Nervous system disorders
Dysgeusia
|
22.2%
4/18 • Number of events 8 • Up to 24 months
|
12.5%
2/16 • Number of events 4 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Nervous system disorders
Headache
|
22.2%
4/18 • Number of events 4 • Up to 24 months
|
6.2%
1/16 • Number of events 3 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
11.1%
2/18 • Number of events 3 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Endocrine disorders
Hypothyroidism
|
11.1%
2/18 • Number of events 3 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Psychiatric disorders
Anxiety
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
18.8%
3/16 • Number of events 3 • Up to 24 months
|
50.0%
2/4 • Number of events 2 • Up to 24 months
|
|
Vascular disorders
Hot Flashes
|
22.2%
4/18 • Number of events 4 • Up to 24 months
|
12.5%
2/16 • Number of events 2 • Up to 24 months
|
25.0%
1/4 • Number of events 1 • Up to 24 months
|
|
Gastrointestinal disorders
Dysphagia
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
18.8%
3/16 • Number of events 3 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Stomach Pain
|
0.00%
0/18 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
25.0%
1/4 • Number of events 1 • Up to 24 months
|
|
General disorders
Non-cardiac chest pain
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
50.0%
2/4 • Number of events 2 • Up to 24 months
|
|
General disorders
Edema limbs
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Reproductive system and breast disorders
Breast Pain
|
16.7%
3/18 • Number of events 3 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
3/18 • Number of events 3 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
50.0%
2/4 • Number of events 3 • Up to 24 months
|
|
Investigations
Hypokalemia
|
16.7%
3/18 • Number of events 4 • Up to 24 months
|
12.5%
2/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Hyponatremia
|
5.6%
1/18 • Number of events 2 • Up to 24 months
|
6.2%
1/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
22.2%
4/18 • Number of events 4 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
General disorders
Fever
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Nervous system disorders
Stroke
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Hypophosphatemia
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Neutropenia
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
6.2%
1/16 • Number of events 1 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Alkaline phosphatase increased
|
11.1%
2/18 • Number of events 2 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
1/18 • Number of events 2 • Up to 24 months
|
6.2%
1/16 • Number of events 2 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
|
Gastrointestinal disorders
Colitis
|
5.6%
1/18 • Number of events 1 • Up to 24 months
|
0.00%
0/16 • Up to 24 months
|
0.00%
0/4 • Up to 24 months
|
Additional Information
Dr. Pamela Munster, MD
University of California, San Francisco
Phone: (415) 502-3598
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place