Trial Outcomes & Findings for Pembrolizumab and GM-CSF in Biliary Cancer (NCT NCT02703714)
NCT ID: NCT02703714
Last Updated: 2022-01-25
Results Overview
Proportion of subjects with measurable disease at study entry who obtained either a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at any time during the course of treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
42 participants
Primary outcome timeframe
Up to 2 years
Results posted on
2022-01-25
Participant Flow
Participant milestones
| Measure |
Pembrolizumab and GM-CSF
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Overall Study
STARTED
|
42
|
|
Overall Study
COMPLETED
|
42
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pembrolizumab and GM-CSF in Biliary Cancer
Baseline characteristics by cohort
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Age, Customized
30-39 years old
|
1 Participants
n=5 Participants
|
|
Age, Customized
40-49 years old
|
3 Participants
n=5 Participants
|
|
Age, Customized
50-59 years old
|
15 Participants
n=5 Participants
|
|
Age, Customized
60-69 years old
|
12 Participants
n=5 Participants
|
|
Age, Customized
70-79 years old
|
10 Participants
n=5 Participants
|
|
Age, Customized
80-89 years old
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
39 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
42 participants
n=5 Participants
|
|
Biliary Cancer Sub-types
Intrahepatic Cholangiocarcinoma (ICC)
|
28 Participants
n=5 Participants
|
|
Biliary Cancer Sub-types
Extrahepatic Cholangiocarcinoma (ECC)
|
11 Participants
n=5 Participants
|
|
Biliary Cancer Sub-types
Gallbladder Cancers (GBC)
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 2 yearsProportion of subjects with measurable disease at study entry who obtained either a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at any time during the course of treatment.
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Overall Response Rate (ORR)
|
0.12 proportion of participants
Interval 0.04 to 0.26
|
SECONDARY outcome
Timeframe: During study treatment and for 30 days after last dose or until start of new treatment (up to 2 years)Safety events will be summarized based on proportion of total subjects, by preferred term. Only treatment-related \>=grade 3 Adverse Events (AE)s will be reported.
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Proportion of Participants With Treatment-related AEs
|
0.095 proportion of participants
Interval 0.03 to 0.23
|
SECONDARY outcome
Timeframe: Up to 4 yearsPopulation: Only 28 participants had lab data collected for this endpoint
PD-L1 expression will be measured by immunohistochemistry (IHC) and classified as positive or negative by central laboratory testing (QualTek Laboratories) using pre-specified cut-points; will be reported along with 95% confidence interval (CI)
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=28 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Proportion of Participants With PD-L1 Positive Status
|
0.36 proportion of participants
Interval 0.19 to 0.56
|
SECONDARY outcome
Timeframe: 6 months after start of study treatmentProportion of participants with PFS Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Proportion of Participants With Progression-Free Survival (PFS) at 6 Months
|
0.26 proportion of participants
Interval 0.14 to 0.42
|
SECONDARY outcome
Timeframe: Within 4 years after start of study treatmentPopulation: Only 5 participants demonstrated an overall response
Time from first documented evidence of CR or PR until the first documented sign of disease progression or death
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=5 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median Duration of Response
|
294 days
Interval 144.0 to 1379.0
|
SECONDARY outcome
Timeframe: Within 4 years after start of study treatmentPopulation: Only 5 participants demonstrated a response of CR or PR, and all participants were diagnosed with Intrahepatic Cholangiocarcinoma (ICC)
Time from first documented evidence of CR or PR until the first documented sign of disease progression or death stratified by sub-type of biliary cancer
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=5 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median Duration of Response Stratified by Sub-type of Biliary Cancer
Intrahepatic Cholangiocarcinoma (ICC)
|
294 days
Interval 144.0 to 1379.0
|
SECONDARY outcome
Timeframe: Within 4 years after start of study treatmentTime from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median Progression Free-Survival (PFS)
|
63 days
Interval 55.0 to 125.0
|
SECONDARY outcome
Timeframe: Within 4 years after start of study treatmentPopulation: Results are reported by sub-type of biliary cancer
Time from date of first dose of protocol therapy to date of first documented radiographic and/or clinical disease progression per RECIST version 1.1 or death from any cause stratified by sub-type of biliary cancer
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median PFS Stratified by Sub-type of Biliary Cancer
Intrahepatic Cholangiocarcinoma (ICC)
|
63 days
Interval 53.0 to 175.0
|
|
Median PFS Stratified by Sub-type of Biliary Cancer
Extrahepatic Cholangiocarcinoma (ECC)
|
58 days
Interval 53.0 to 151.0
|
|
Median PFS Stratified by Sub-type of Biliary Cancer
Gallbladder Cancer (GBC)
|
121 days
Interval 57.0 to 132.0
|
SECONDARY outcome
Timeframe: Within 4 years after start of treatmentTime from first dose of protocol therapy to the date of death due to any cause
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median Overall Survival (OS)
|
393 days
Interval 243.0 to 573.0
|
SECONDARY outcome
Timeframe: Within 4 years after start of treatmentPopulation: Results are reported by sub-type of biliary cancer
Time from first dose of protocol therapy to the date of death due to any cause stratified by sub-type of biliary cancer.
Outcome measures
| Measure |
Pembrolizumab and GM-CSF
n=42 Participants
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer
Intrahepatic Cholangiocarcinoma (ICC)
|
424 days
Interval 295.0 to 1033.0
|
|
Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer
Extrahepatic Cholangiocarcinoma (ECC)
|
286 days
Interval 108.0 to 623.0
|
|
Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer
Gallbladder Cancers (GBC)
|
165 days
Interval 156.0 to 393.0
|
Adverse Events
Pembrolizumab and GM-CSF
Serious events: 18 serious events
Other events: 42 other events
Deaths: 37 deaths
Serious adverse events
| Measure |
Pembrolizumab and GM-CSF
n=42 participants at risk
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.4%
1/42 • Number of events 2 • Up to 4 years
|
|
Infections and infestations
Biliary tract infection
|
9.5%
4/42 • Number of events 8 • Up to 4 years
|
|
General disorders
Fever
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Infections and infestations
Sepsis
|
4.8%
2/42 • Number of events 2 • Up to 4 years
|
|
Vascular disorders
Hypotension
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Enterocolitis
|
2.4%
1/42 • Number of events 2 • Up to 4 years
|
|
Psychiatric disorders
Delirium
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Investigations
Aspartate aminotransferase increased
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Investigations
Alanine aminotransferase increased
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Infections and infestations
Lung Infection
|
4.8%
2/42 • Number of events 2 • Up to 4 years
|
|
Hepatobiliary disorders
Hepatic Hemorrhage
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Ascities
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Hepatobiliary disorders
Bile duct stenosis
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Hepatobiliary disorders
Cholangitis
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Nausea
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Colitis
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Abdominal Distension
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Metabolism and nutrition disorders
Dehydration
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Gastrointestinal disorders
Abdominal Pain
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Endocrine disorders
Hyperthyroidism
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
|
Eye disorders
Extraocular muscle paresis
|
2.4%
1/42 • Number of events 1 • Up to 4 years
|
Other adverse events
| Measure |
Pembrolizumab and GM-CSF
n=42 participants at risk
Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
42.9%
18/42 • Number of events 23 • Up to 4 years
|
|
Gastrointestinal disorders
Abdominal pain
|
40.5%
17/42 • Number of events 28 • Up to 4 years
|
|
Gastrointestinal disorders
Nausea
|
28.6%
12/42 • Number of events 17 • Up to 4 years
|
|
Gastrointestinal disorders
Ascites
|
26.2%
11/42 • Number of events 15 • Up to 4 years
|
|
Gastrointestinal disorders
Constipation
|
21.4%
9/42 • Number of events 9 • Up to 4 years
|
|
Gastrointestinal disorders
Vomiting
|
19.0%
8/42 • Number of events 9 • Up to 4 years
|
|
Gastrointestinal disorders
Abdominal distension
|
9.5%
4/42 • Number of events 4 • Up to 4 years
|
|
Gastrointestinal disorders
Dry mouth
|
11.9%
5/42 • Number of events 6 • Up to 4 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
11.9%
5/42 • Number of events 7 • Up to 4 years
|
|
Gastrointestinal disorders
Bloating
|
9.5%
4/42 • Number of events 4 • Up to 4 years
|
|
Gastrointestinal disorders
Dyspepsia
|
9.5%
4/42 • Number of events 4 • Up to 4 years
|
|
Gastrointestinal disorders
Flatulence
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
General disorders
Fatigue
|
45.2%
19/42 • Number of events 29 • Up to 4 years
|
|
General disorders
Fever
|
33.3%
14/42 • Number of events 28 • Up to 4 years
|
|
General disorders
Injection site reaction
|
33.3%
14/42 • Number of events 16 • Up to 4 years
|
|
General disorders
Chills
|
28.6%
12/42 • Number of events 13 • Up to 4 years
|
|
General disorders
Edema limbs
|
21.4%
9/42 • Number of events 11 • Up to 4 years
|
|
General disorders
General disorders and administration site conditions - Other
|
11.9%
5/42 • Number of events 5 • Up to 4 years
|
|
General disorders
Non-cardiac chest pain
|
11.9%
5/42 • Number of events 5 • Up to 4 years
|
|
Blood and lymphatic system disorders
Leukocytosis
|
71.4%
30/42 • Number of events 47 • Up to 4 years
|
|
Blood and lymphatic system disorders
Anemia
|
9.5%
4/42 • Number of events 9 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
14/42 • Number of events 22 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
28.6%
12/42 • Number of events 13 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.4%
9/42 • Number of events 11 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
19.0%
8/42 • Number of events 9 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.9%
5/42 • Number of events 8 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
35.7%
15/42 • Number of events 25 • Up to 4 years
|
|
Metabolism and nutrition disorders
Anorexia
|
23.8%
10/42 • Number of events 12 • Up to 4 years
|
|
Metabolism and nutrition disorders
Dehydration
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
31.0%
13/42 • Number of events 17 • Up to 4 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
31.0%
13/42 • Number of events 20 • Up to 4 years
|
|
Investigations
Weight loss
|
26.2%
11/42 • Number of events 14 • Up to 4 years
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
7/42 • Number of events 14 • Up to 4 years
|
|
Investigations
Blood bilirubin increased
|
14.3%
6/42 • Number of events 9 • Up to 4 years
|
|
Investigations
Creatinine increased
|
14.3%
6/42 • Number of events 6 • Up to 4 years
|
|
Investigations
Platelet count decreased
|
14.3%
6/42 • Number of events 10 • Up to 4 years
|
|
Investigations
Alanine aminotransferase increased
|
9.5%
4/42 • Number of events 12 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
31.0%
13/42 • Number of events 18 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.1%
3/42 • Number of events 4 • Up to 4 years
|
|
Infections and infestations
Upper respiratory infection
|
23.8%
10/42 • Number of events 16 • Up to 4 years
|
|
Infections and infestations
Urinary tract infection
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
16.7%
7/42 • Number of events 9 • Up to 4 years
|
|
Infections and infestations
Dizziness
|
9.5%
4/42 • Number of events 4 • Up to 4 years
|
|
Endocrine disorders
Hypothyroidism
|
19.0%
8/42 • Number of events 10 • Up to 4 years
|
|
Endocrine disorders
Hyperthyroidism
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Cardiac disorders
Palpitations
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Vascular disorders
Thromboembolic event
|
9.5%
4/42 • Number of events 5 • Up to 4 years
|
|
Injury, poisoning and procedural complications
Fall
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Renal and urinary disorders
Urinary frequency
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Eye disorders
Dry eye
|
11.9%
5/42 • Number of events 6 • Up to 4 years
|
|
Psychiatric disorders
Depression
|
7.1%
3/42 • Number of events 4 • Up to 4 years
|
|
Psychiatric disorders
Confusion
|
7.1%
3/42 • Number of events 3 • Up to 4 years
|
|
Psychiatric disorders
Insomnia
|
9.5%
4/42 • Number of events 6 • Up to 4 years
|
Additional Information
Dr. R. Katie Kelley, MD
University of California, San Francisco
Phone: (415) 353-9888
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place