Pembrolizumab and GM-CSF in Biliary Cancer

• Sponsor: Robin Kate Kelley (Other)
• Overall Status: Completed
• CT.gov ID: NCT02703714
• Collaborator: American Society of Clinical Oncology (Other), Merck Sharp & Dohme LLC (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 42
• Location: 1
• Arm: 1
• Actual Duration (Months): 55.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is an open label phase II trial to examine efficacy and safety of a novel combination of pembrolizumab plus induction GM-CSF in patients with advanced biliary cancers treated at University of California, San Francisco (UCSF).

This phase II study will examine the efficacy and safety of the novel combination of pembrolizumab plus induction GM-CSF in advanced biliary cancer patients with the hypotheses that the combination may increase proportion of patients with overall response compared to contemporary historical controls, with acceptable safety.

Condition or Disease	Intervention/Treatment	Phase
Biliary Cancer	Drug: Pembrolizumab; Drug: Sargramostim	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Pembrolizumab (MK-3475) With GM-CSF Induction in Advanced Biliary Cancers
• Actual Study Start Date: May 6, 2016
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Pembrolizumab; 200 mg given intravenously (IV); Other Names: MK-3475 Keytruda ; Drug: Sargramostim; 250 µg given subcutaneously (SC); Other Names: GM-CSF

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Up to 2 years]

   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.

Secondary Outcome Measures

1. Proportion of Participants With Treatment-related AEs [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.

2. Proportion of Participants With PD-L1 Positive Status [Up to 4 years]

   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)

3. Proportion of Participants With Progression-Free Survival (PFS) at 6 Months [6 months after start of study treatment]

   Proportion 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

4. Median Duration of Response [Within 4 years after start of study treatment]

   Time from first documented evidence of CR or PR until the first documented sign of disease progression or death

5. Median Duration of Response Stratified by Sub-type of Biliary Cancer [Within 4 years after start of study treatment]

   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

6. Median Progression Free-Survival (PFS) [Within 4 years after start of study treatment]

   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

7. Median PFS Stratified by Sub-type of Biliary Cancer [Within 4 years after start of study treatment]

   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

8. Median Overall Survival (OS) [Within 4 years after start of treatment]

   Time from first dose of protocol therapy to the date of death due to any cause

9. Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer [Within 4 years after start of treatment]

   Time from first dose of protocol therapy to the date of death due to any cause stratified by sub-type of biliary cancer.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be willing and able to provide written informed consent for the trial.

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

• Demonstrate adequate organ function

• Absolute neutrophil count (ANC) >= 1,000/microliter (mcL)(performed within 28 days of treatment initiation)

• Platelets >= 60,000/mcL (>= 75,000/mcL in expansion cohort) (performed within 28 days of treatment initiation)

• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation)

• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 28 days of treatment initiation)

• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 28 days of treatment initiation)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 5 X ULN (performed within 28 days of treatment initiation)

• Albumin >= 2.5 mg/dL (performed within 28 days of treatment initiation)

• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)

• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)

• Patients with known hepatitis B (HBV) or hepatitis C virus (HCV) infection are eligible provided liver function parameters meet laboratory eligibility criteria

• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication

• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

ADDITIONAL EXPANSION COHORT SUBJECT INCLUSION CRITERIA

• Tumor measurable by RECIST 1.1 including >= 1 target lesion not planned for biopsy

• Presence of >= 1 tumor lesion not included as a RECIST 1.1 target lesion which is assessed by investigator and/or radiologist as likely to be amenable to percutaneous biopsy by punch, computed tomography (CT)-, or ultrasound-guided core needle biopsy for serial sampling on treatment

• Platelet count >= 75,000/mcL

• No contraindication to tumor biopsy at time of study enrollment

• Consent for on-treatment paired biopsies

Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated and received study therapy in a study of an investigational agent, or used an investigational device within 4 weeks of the first dose of treatment.

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy for purposes of immunosuppression or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

• Has a known history of active Bacillus Tuberculosis (TB).

• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

• Has untreated active Hepatitis B (e.g., HBsAg reactive).

• Has an active infection requiring systemic antibiotic therapy at time of enrollment.

• Treatment with antibiotic prophylaxis for indwelling biliary stent(s) or peri-procedural antibiotics for uncomplicated biliary stent exchanges is allowed and not an exclusion

• Hypersensitivity to pembrolizumab or any of its excipients.

• Has received treatment with an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

• Has received treatment with chemotherapy, targeted small molecule therapy, or radiation therapy to non-liver sites within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent administered more than 2 weeks earlier.

• Has had prior chemoembolization, bland embolization, radioembolization, local ablative therapies, radiation to liver tumors, or major surgery such as liver resection within 4 weeks prior to study enrollment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to intervention more than 4 weeks earlier.

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.

• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

• Has known history of or any evidence of active, non-infectious pneumonitis.

• Has had prior liver or other organ transplantation.

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

• Has received a live vaccine within 30 days of planned start of study therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94158

Sponsors and Collaborators

• Robin Kate Kelley
• American Society of Clinical Oncology
• Merck Sharp & Dohme LLC
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: R. Kate Kelley, M.D., University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 1, 2019

More Information

Publications

None provided.

• Responsible Party: Robin Kate Kelley, Associate Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02703714
• Other Study ID Numbers: 154524; NCI-2017-01372; R03CA212877
• First Posted: Mar 9, 2016
• Last Update Posted: Jan 25, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Robin Kate Kelley, Associate Professor, University of California, San Francisco: Advanced; Locally-advanced; Not eligible for resection; Prior chemotherapy treatment
• Additional relevant MeSH terms: Biliary Tract Neoplasms; Pembrolizumab; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Period Title: Overall Study
STARTED	42
COMPLETED	42
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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 Participants	42
Age, Customized (Count of Participants)
30-39 years old	1 2.4%
40-49 years old	3 7.1%
50-59 years old	15 35.7%
60-69 years old	12 28.6%
70-79 years old	10 23.8%
80-89 years old	1 2.4%
Sex: Female, Male (Count of Participants)
Female	24 57.1%
Male	18 42.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 7.1%
Not Hispanic or Latino	39 92.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	9 21.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.4%
White	30 71.4%
More than one race	0 0%
Unknown or Not Reported	2 4.8%
Region of Enrollment (participants) [Number]
United States	42 100%
Biliary Cancer Sub-types (Count of Participants)
Intrahepatic Cholangiocarcinoma (ICC)	28 66.7%
Extrahepatic Cholangiocarcinoma (ECC)	11 26.2%
Gallbladder Cancers (GBC)	3 7.1%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Number (95% Confidence Interval) [proportion of participants]	0.12 0.3%

2. Secondary Outcome

Title	Proportion of Participants With Treatment-related AEs
Description	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.
Time Frame	During study treatment and for 30 days after last dose or until start of new treatment (up to 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Number (95% Confidence Interval) [proportion of participants]	0.095 0.2%

3. Secondary Outcome

Title	Proportion of Participants With PD-L1 Positive Status
Description	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)
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Only 28 participants had lab data collected for this endpoint

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	28
Number (95% Confidence Interval) [proportion of participants]	0.36 0.9%

4. Secondary Outcome

Title	Proportion of Participants With Progression-Free Survival (PFS) at 6 Months
Description	Proportion 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
Time Frame	6 months after start of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Number (95% Confidence Interval) [proportion of participants]	0.26 0.6%

5. Secondary Outcome

Title	Median Duration of Response
Description	Time from first documented evidence of CR or PR until the first documented sign of disease progression or death
Time Frame	Within 4 years after start of study treatment

Outcome Measure Data

Analysis Population Description

Only 5 participants demonstrated an overall response

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	5
Median (Full Range) [days]	294

6. Secondary Outcome

Title	Median Duration of Response Stratified by Sub-type of Biliary Cancer
Description	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
Time Frame	Within 4 years after start of study treatment

Outcome Measure Data

Analysis Population Description

Only 5 participants demonstrated a response of CR or PR, and all participants were diagnosed with Intrahepatic Cholangiocarcinoma (ICC)

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	5
Intrahepatic Cholangiocarcinoma (ICC)	294

7. Secondary Outcome

Title	Median Progression Free-Survival (PFS)
Description	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
Time Frame	Within 4 years after start of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Median (95% Confidence Interval) [days]	63

8. Secondary Outcome

Title	Median PFS Stratified by Sub-type of Biliary Cancer
Description	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
Time Frame	Within 4 years after start of study treatment

Outcome Measure Data

Analysis Population Description

Results are reported by sub-type of biliary cancer

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Intrahepatic Cholangiocarcinoma (ICC)	63
Extrahepatic Cholangiocarcinoma (ECC)	58
Gallbladder Cancer (GBC)	121

9. Secondary Outcome

Title	Median Overall Survival (OS)
Description	Time from first dose of protocol therapy to the date of death due to any cause
Time Frame	Within 4 years after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Median (95% Confidence Interval) [days]	393

10. Secondary Outcome

Title	Median Overall Survival (OS) Stratified by Sub-type of Biliary Cancer
Description	Time from first dose of protocol therapy to the date of death due to any cause stratified by sub-type of biliary cancer.
Time Frame	Within 4 years after start of treatment

Outcome Measure Data

Analysis Population Description

Results are reported by sub-type of biliary cancer

Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
Measure Participants	42
Intrahepatic Cholangiocarcinoma (ICC)	424
Extrahepatic Cholangiocarcinoma (ECC)	286
Gallbladder Cancers (GBC)	165

Adverse Events

Time Frame	Up to 4 years
Arm/Group Title	Pembrolizumab and GM-CSF
Arm/Group Description	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.
All Cause Mortality
	Pembrolizumab and GM-CSF
	Affected / at Risk (%)	# Events
Total	37/42 (88.1%)
Serious Adverse Events
	Pembrolizumab and GM-CSF
	Affected / at Risk (%)	# Events
Total	18/42 (42.9%)
Endocrine disorders
Hyperthyroidism	1/42 (2.4%)	1
Eye disorders
Extraocular muscle paresis	1/42 (2.4%)	1
Gastrointestinal disorders
Enterocolitis	1/42 (2.4%)	2
Ascities	1/42 (2.4%)	1
Nausea	1/42 (2.4%)	1
Colitis	1/42 (2.4%)	1
Abdominal Distension	1/42 (2.4%)	1
Abdominal Pain	1/42 (2.4%)	1
General disorders
Fever	4/42 (9.5%)	5
Hepatobiliary disorders
Hepatic Hemorrhage	1/42 (2.4%)	1
Bile duct stenosis	1/42 (2.4%)	1
Cholangitis	1/42 (2.4%)	1
Hepatobiliary disorders - Other	1/42 (2.4%)	1
Infections and infestations
Biliary tract infection	4/42 (9.5%)	8
Sepsis	2/42 (4.8%)	2
Lung Infection	2/42 (4.8%)	2
Investigations
Aspartate aminotransferase increased	1/42 (2.4%)	1
Alanine aminotransferase increased	1/42 (2.4%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/42 (2.4%)	2
Dehydration	1/42 (2.4%)	1
Psychiatric disorders
Delirium	1/42 (2.4%)	1
Vascular disorders
Hypotension	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab and GM-CSF
	Affected / at Risk (%)	# Events
Total	42/42 (100%)
Blood and lymphatic system disorders
Leukocytosis	30/42 (71.4%)	47
Anemia	4/42 (9.5%)	9
Cardiac disorders
Palpitations	3/42 (7.1%)	3
Endocrine disorders
Hypothyroidism	8/42 (19%)	10
Hyperthyroidism	4/42 (9.5%)	5
Eye disorders
Dry eye	5/42 (11.9%)	6
Gastrointestinal disorders
Diarrhea	18/42 (42.9%)	23
Abdominal pain	17/42 (40.5%)	28
Nausea	12/42 (28.6%)	17
Ascites	11/42 (26.2%)	15
Constipation	9/42 (21.4%)	9
Vomiting	8/42 (19%)	9
Abdominal distension	4/42 (9.5%)	4
Dry mouth	5/42 (11.9%)	6
Gastrointestinal disorders - Other	5/42 (11.9%)	7
Bloating	4/42 (9.5%)	4
Dyspepsia	4/42 (9.5%)	4
Flatulence	3/42 (7.1%)	3
General disorders
Fatigue	19/42 (45.2%)	29
Fever	14/42 (33.3%)	28
Injection site reaction	14/42 (33.3%)	16
Chills	12/42 (28.6%)	13
Edema limbs	9/42 (21.4%)	11
General disorders and administration site conditions - Other	5/42 (11.9%)	5
Non-cardiac chest pain	5/42 (11.9%)	5
Infections and infestations
Upper respiratory infection	10/42 (23.8%)	16
Urinary tract infection	4/42 (9.5%)	5
Dizziness	4/42 (9.5%)	4
Injury, poisoning and procedural complications
Fall	3/42 (7.1%)	3
Investigations
Weight loss	11/42 (26.2%)	14
Aspartate aminotransferase increased	7/42 (16.7%)	14
Blood bilirubin increased	6/42 (14.3%)	9
Creatinine increased	6/42 (14.3%)	6
Platelet count decreased	6/42 (14.3%)	10
Alanine aminotransferase increased	4/42 (9.5%)	12
Metabolism and nutrition disorders
Hypoalbuminemia	15/42 (35.7%)	25
Anorexia	10/42 (23.8%)	12
Dehydration	3/42 (7.1%)	3
Hypokalemia	4/42 (9.5%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	14/42 (33.3%)	22
Myalgia	12/42 (28.6%)	13
Back pain	9/42 (21.4%)	11
Bone pain	8/42 (19%)	9
Pain in extremity	5/42 (11.9%)	8
Flank pain	4/42 (9.5%)	5
Chest wall pain	3/42 (7.1%)	3
Nervous system disorders
Peripheral sensory neuropathy	7/42 (16.7%)	9
Psychiatric disorders
Depression	3/42 (7.1%)	4
Confusion	3/42 (7.1%)	3
Insomnia	4/42 (9.5%)	6
Renal and urinary disorders
Urinary frequency	3/42 (7.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	13/42 (31%)	18
Dyspnea	3/42 (7.1%)	3
Nasal congestion	3/42 (7.1%)	4
Skin and subcutaneous tissue disorders
Pruritus	13/42 (31%)	17
Rash maculo-papular	13/42 (31%)	20
Vascular disorders
Thromboembolic event	4/42 (9.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.