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)
42
1
1
55.9
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
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)

    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    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
    Adverse Event Reporting Description
    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.

    Results Point of Contact

    Name/Title Dr. R. Katie Kelley, MD
    Organization University of California, San Francisco
    Phone (415) 353-9888
    Email katie.kelley@ucsf.edu
    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