KEYNOTE145: ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02362035
Collaborator
Merck Sharp & Dohme LLC (Industry)
161
19
1
130.3
8.5
0.1

Study Details

Study Description

Brief Summary

This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.

Detailed Description

This is a Phase 1b/2, open-label, nonrandomized study that will be conducted in 2 stages. In the first stage, Part 1 of the study will determine the safety and preliminary efficacy of acalabrutinib and pembrolizumab in a limited group of B-cell malignancies. In the second stage, Part 2 allows for possible expansion cohorts into a wider range of B-cell malignancies, and Part 3 will evaluate the combination in subjects with myelofibrosis (MF).

Study Design

Study Type:
Interventional
Actual Enrollment :
161 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
Actual Study Start Date :
Feb 20, 2015
Actual Primary Completion Date :
Jul 14, 2020
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Acalabrutinib plus Pembrolizumab

A nonrandomized study that will be conducted in 2 stages. In the first stage, (Safety), subjects will receive Acalabrutinib Dose A orally administered (PO) twice daily (BID) in combination with Pembrolizumab Dose B administered every 3 weeks (Q3W). The second stage was an expansion of Cohorts with the same dose regimen as the first stage. An additional expansion in subjects with Myelofibrosis was planned but not conducted.

Drug: Acalabrutinib
Orally Administered (PO)
Other Names:
  • ACP-196
  • Drug: Pembrolizumab
    Intravenous Administered (IV)
    Other Names:
  • KEYTRUDA
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment Emergent Adverse Events (AEs) [104 weeks]

      Treatment-emergent AEs were defined as those events that occurred on or after the first dose of study drug, through the treatment phase, and within 30 days following the last dose of study drug.

    2. Number of Participants With Grade 3-4 Adverse Events [104 weeks]

      Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03

    3. Number of Participants With Grade 5 Adverse Events [104 weeks]

      Number of participants with CTCAE Grade 5 (fatal) adverse events

    4. Number of Participants With Any Study-Drug Related AE [104 weeks]

      Study drug-related AEs were those assessed by investigator as related to study treatment.

    5. Number of Participants With Grade 3-4 Study-Drug Related AE [104 weeks]

      The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.

    6. Number of Participants With Grade 5 Study-Drug Related AE [104 weeks]

      Grade 5 (fatal) AEs assessed by investigator as related to study treatment.

    7. Number of Participants With Any SAE [104 weeks]

      Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.

    8. Number of Participants With Grade 3-4 Any SAE [104 weeks]

      Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.

    9. Number of Participants With Grade 5 Any SAE [104 weeks]

      Grade 5 events were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.

    10. Number of Participants With Any Study Drug-Related SAE [104 weeks]

      Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.

    11. Number of Participants With Any Grade 3-4 Study Drug-Related SAE [104 weeks]

      Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.

    12. Number of Participants With Any Grade 5 Study Drug-Related SAE [104 weeks]

      Grade 5 AEs were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.

    13. Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay [104 weeks]

      AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.

    14. Number of Participants With AE Leading to Study Drug Discontinuation [104 weeks]

      An adverse event that resulted in the permanent discontinuation of study treatment in the study.

    15. Number of Participants With AE Leading to Study Drug Delay [104 weeks]

      An adverse event that caused a temporary withholding of study treatment.

    16. Number of Participants With AE Leading to Study Drug Modification [104 weeks]

      An adverse event that resulted in a reduction in the dosage of study treatment for that participant.

    Secondary Outcome Measures

    1. Overall Response Rate [104 weeks]

      The percentage of subjects who achieve a partial response or complete response

    2. Duration of Response [104 weeks]

      The interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause

    3. Progression-free Survival [104 weeks]

      The interval from the first dose date of acalabrutinib or pembrolizumab to the earlier of the first documentation of objective disease progression or death from any cause

    4. Overall Survival [104 weeks]

      The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause

    5. Time to Next Treatment [104 weeks]

      The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Main Inclusion Criteria:
    • Diagnosis of a hematologic malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO).

    • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

    • Agreement to use contraception during the study and for 90 days after the last dose of ACP-196 or 120 days after the last dose of pembrolizumab, if sexually active and able to bear or beget children.

    • Completion of all therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 4 weeks before the start of study therapy.

    • ANC ≥ 0.5 x 109/L or platelet count ≥ 50 x 109/L unless due to disease involvement in the bone marrow.

    Main Exclusion Criteria:
    • A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of study drugs, or put the study outcomes at undue risk.

    • Central nervous system (CNS) involvement by lymphoma/leukemia

    • Any therapeutic antibody within 4 weeks of first dose of study drugs.

    • Total bilirubin > 1.5 x ULN; and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN.

    • Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Tucson Arizona United States 85704
    2 Research Site Los Angeles California United States 90095
    3 Research Site Denver Colorado United States 80218
    4 Research Site Washington District of Columbia United States 20007
    5 Research Site Niles Illinois United States 60714
    6 Research Site Boston Massachusetts United States 2215
    7 Research Site Rochester Minnesota United States 55905-0001
    8 Research Site Omaha Nebraska United States 68198-7680
    9 Research Site Columbus Ohio United States 43210
    10 Research Site Greenville South Carolina United States 29605
    11 Research Site Nashville Tennessee United States 37203
    12 Research Site Dallas Texas United States 75246
    13 Research Site Houston Texas United States 77030
    14 Research Site San Antonio Texas United States 78217
    15 Research Site Tyler Texas United States 75702
    16 Research Site Fairfax Virginia United States 22031
    17 Research Site Roanoke Virginia United States 24014
    18 Research Site Vancouver Washington United States 98684
    19 Research Site Yakima Washington United States 98902

    Sponsors and Collaborators

    • Acerta Pharma BV
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: AstraZeneca Clinical Study Information Center, 1-877-240-9479 - information.center@astrazeneca.com

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02362035
    Other Study ID Numbers:
    • ACE-LY-005
    First Posted:
    Feb 12, 2015
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jul 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail For the ACE-LY-005 program, Study Terminated by Sponsor refers to the following: Patients receiving treatment benefits will continue to be provided with study medication in the Post Final Analysis Management of the trial. No further data collection for analysis and reporting will be completed after the final Analysis
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Period Title: Overall Study
    STARTED 161
    COMPLETED 0
    NOT COMPLETED 161

    Baseline Characteristics

    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Overall Participants 161
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    62.4
    (14.6)
    Sex: Female, Male (Count of Participants)
    Female
    63
    39.1%
    Male
    98
    60.9%
    Race/Ethnicity, Customized (Number) [Number]
    Hispanic or Latino
    11
    6.8%
    Not Hispanic or Latino
    148
    91.9%
    Not Reported
    2
    1.2%
    Race/Ethnicity, Customized (Number) [Number]
    American Indian or Alaska Native
    0
    0%
    Asian
    4
    2.5%
    Black or African American
    5
    3.1%
    Native Hawaiian or Other Pacific Islander
    2
    1.2%
    White
    141
    87.6%
    Not Reported
    9
    5.6%
    Region of Enrollment (Number) [Number]
    USA
    161
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment Emergent Adverse Events (AEs)
    Description Treatment-emergent AEs were defined as those events that occurred on or after the first dose of study drug, through the treatment phase, and within 30 days following the last dose of study drug.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    160
    99.4%
    2. Primary Outcome
    Title Number of Participants With Grade 3-4 Adverse Events
    Description Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    105
    65.2%
    3. Primary Outcome
    Title Number of Participants With Grade 5 Adverse Events
    Description Number of participants with CTCAE Grade 5 (fatal) adverse events
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    9
    5.6%
    4. Primary Outcome
    Title Number of Participants With Any Study-Drug Related AE
    Description Study drug-related AEs were those assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    142
    88.2%
    5. Primary Outcome
    Title Number of Participants With Grade 3-4 Study-Drug Related AE
    Description The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    66
    41%
    6. Primary Outcome
    Title Number of Participants With Grade 5 Study-Drug Related AE
    Description Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    3
    1.9%
    7. Primary Outcome
    Title Number of Participants With Any SAE
    Description Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    75
    46.6%
    8. Primary Outcome
    Title Number of Participants With Grade 3-4 Any SAE
    Description Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    64
    39.8%
    9. Primary Outcome
    Title Number of Participants With Grade 5 Any SAE
    Description Grade 5 events were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    9
    5.6%
    10. Primary Outcome
    Title Number of Participants With Any Study Drug-Related SAE
    Description Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    34
    21.1%
    11. Primary Outcome
    Title Number of Participants With Any Grade 3-4 Study Drug-Related SAE
    Description Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher. Drug-related AEs were those assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    30
    18.6%
    12. Primary Outcome
    Title Number of Participants With Any Grade 5 Study Drug-Related SAE
    Description Grade 5 AEs were fatal events. Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment. Drug-related AEs were those assessed by investigator as related to study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    3
    1.9%
    13. Primary Outcome
    Title Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay
    Description AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    83
    51.6%
    14. Primary Outcome
    Title Number of Participants With AE Leading to Study Drug Discontinuation
    Description An adverse event that resulted in the permanent discontinuation of study treatment in the study.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    45
    28%
    15. Primary Outcome
    Title Number of Participants With AE Leading to Study Drug Delay
    Description An adverse event that caused a temporary withholding of study treatment.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    71
    44.1%
    16. Primary Outcome
    Title Number of Participants With AE Leading to Study Drug Modification
    Description An adverse event that resulted in a reduction in the dosage of study treatment for that participant.
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the safety of the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number [Number of participants]
    9
    5.6%
    17. Secondary Outcome
    Title Overall Response Rate
    Description The percentage of subjects who achieve a partial response or complete response
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Number (95% Confidence Interval) [percent]
    38.5
    18. Secondary Outcome
    Title Duration of Response
    Description The interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Median (95% Confidence Interval) [Months]
    28.5
    19. Secondary Outcome
    Title Progression-free Survival
    Description The interval from the first dose date of acalabrutinib or pembrolizumab to the earlier of the first documentation of objective disease progression or death from any cause
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Median (95% Confidence Interval) [Months]
    4.7
    20. Secondary Outcome
    Title Overall Survival
    Description The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Median (95% Confidence Interval) [Months]
    50.4
    21. Secondary Outcome
    Title Time to Next Treatment
    Description The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment
    Time Frame 104 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants in this study received both study drugs and were therefore analyzed together as a single treatment arm. Participants receiving the different regimens were not analyzed separately by regimen, as the study was designed to assess the the combination study treatment.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    Measure Participants 161
    Median (95% Confidence Interval) [Months]
    21.1

    Adverse Events

    Time Frame For each subject, adverse event data were collected from first dose of study drug until 30 days after the last dose, until the end of the study (data cutoff date of 14 July 2020).
    Adverse Event Reporting Description All participants in this study received both study drugs and were analyzed together as a single treatment arm. There were 3 Stages to the study (representing different disease histologies) and not 3 arms in the study. Study data are presented by disease histology for all subjects in Stage 1 (N=30) and Stage 2 (N=131) as TOTAL subjects (N=161). Stage 3 of the study was not conducted.
    Arm/Group Title Acalabrutinib + Pembrolizumab
    Arm/Group Description All participants in this study received both study drugs and were therefore analysed together as a single treatment arm. Participants receiving the different regimens were not analysed separately by regimen, as the study was designed to assess the safety of the combination study treatment. The study included N=161 participants who received both acalabrutinib and pembrolizumab and are summarized together (from First stage safety lead-in and Second stage expansion). Stage 3 (additional expansion in subjects with Myelofibrosis) was planned but not conducted.
    All Cause Mortality
    Acalabrutinib + Pembrolizumab
    Affected / at Risk (%) # Events
    Total 69/161 (42.9%)
    Serious Adverse Events
    Acalabrutinib + Pembrolizumab
    Affected / at Risk (%) # Events
    Total 75/161 (46.6%)
    Blood and lymphatic system disorders
    Anaemia 2/161 (1.2%) 2
    Anaemia of malignant disease 1/161 (0.6%) 1
    Febrile neutropenia 2/161 (1.2%) 2
    Hyperviscosity syndrome 1/161 (0.6%) 1
    Lymphadenitis 1/161 (0.6%) 1
    Cardiac disorders
    Cardiac failure congestive 1/161 (0.6%) 1
    Cardiogenic shock 1/161 (0.6%) 1
    Pericardial effusion 1/161 (0.6%) 1
    Ear and labyrinth disorders
    Vertigo 1/161 (0.6%) 1
    Endocrine disorders
    Hypercalcaemia of malignancy 1/161 (0.6%) 1
    Hypothyroidism 1/161 (0.6%) 1
    Gastrointestinal disorders
    Abdominal pain 2/161 (1.2%) 2
    Colitis 1/161 (0.6%) 1
    Enteritis 1/161 (0.6%) 1
    Gastric haemorrhage 1/161 (0.6%) 3
    Gastric ulcer haemorrhage 1/161 (0.6%) 1
    Gastritis 1/161 (0.6%) 1
    Gastrointestinal haemorrhage 3/161 (1.9%) 3
    Large intestinal obstruction 1/161 (0.6%) 1
    Nausea 2/161 (1.2%) 2
    Pancreatitis 1/161 (0.6%) 1
    Retroperitoneal mass 1/161 (0.6%) 1
    Upper gastrointestinal haemorrhage 2/161 (1.2%) 2
    Vomiting 2/161 (1.2%) 2
    General disorders
    Non-cardiac chest pain 1/161 (0.6%) 1
    Pain 1/161 (0.6%) 1
    Pyrexia 2/161 (1.2%) 2
    Systemic inflammatory response syndrome 2/161 (1.2%) 2
    Hepatobiliary disorders
    Drug-induced liver injury 1/161 (0.6%) 1
    Immune system disorders
    Autoimmune disorder 1/161 (0.6%) 1
    Cytokine release syndrome 1/161 (0.6%) 1
    Infections and infestations
    Abdominal abscess 1/161 (0.6%) 1
    Bacteraemia 1/161 (0.6%) 1
    Bronchitis 1/161 (0.6%) 1
    Cellulitis 1/161 (0.6%) 2
    Epiglottitis 1/161 (0.6%) 1
    Herpes zoster 1/161 (0.6%) 1
    Influenza 2/161 (1.2%) 2
    Meningitis bacterial 1/161 (0.6%) 1
    Necrotising fasciitis 1/161 (0.6%) 1
    Neutropenic sepsis 1/161 (0.6%) 1
    Pneumocystis jirovecii pneumonia 1/161 (0.6%) 1
    Pneumonia 9/161 (5.6%) 9
    Pneumonia mycoplasmal 1/161 (0.6%) 1
    Sepsis 5/161 (3.1%) 5
    Septic shock 2/161 (1.2%) 2
    Staphylococcal bacteraemia 1/161 (0.6%) 1
    Upper respiratory tract infection 1/161 (0.6%) 1
    Injury, poisoning and procedural complications
    Fall 1/161 (0.6%) 1
    Foot fracture 1/161 (0.6%) 1
    Hip fracture 2/161 (1.2%) 2
    Limb injury 1/161 (0.6%) 1
    Investigations
    Alanine aminotransferase increased 3/161 (1.9%) 3
    Aspartate aminotransferase increased 4/161 (2.5%) 4
    Lymphocyte count decreased 1/161 (0.6%) 1
    Platelet count decreased 1/161 (0.6%) 2
    Metabolism and nutrition disorders
    Dehydration 3/161 (1.9%) 3
    Hypercalcaemia 1/161 (0.6%) 1
    Hyponatraemia 3/161 (1.9%) 4
    Lactic acidosis 1/161 (0.6%) 1
    Tumour lysis syndrome 1/161 (0.6%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 2/161 (1.2%) 3
    Musculoskeletal chest pain 1/161 (0.6%) 1
    Musculoskeletal pain 1/161 (0.6%) 1
    Neck pain 1/161 (0.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour flare 1/161 (0.6%) 1
    Nervous system disorders
    Cervical cord compression 1/161 (0.6%) 1
    Headache 1/161 (0.6%) 1
    Hyponatraemic seizure 1/161 (0.6%) 1
    Seizure 1/161 (0.6%) 1
    Syncope 2/161 (1.2%) 3
    Psychiatric disorders
    Mental status changes 3/161 (1.9%) 3
    Renal and urinary disorders
    Acute kidney injury 4/161 (2.5%) 4
    Renal failure 1/161 (0.6%) 1
    Tubulointerstitial nephritis 1/161 (0.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 3/161 (1.9%) 3
    Dyspnoea 1/161 (0.6%) 1
    Pleural effusion 4/161 (2.5%) 4
    Pneumonitis 2/161 (1.2%) 2
    Respiratory disorder 1/161 (0.6%) 1
    Respiratory distress 1/161 (0.6%) 1
    Respiratory failure 1/161 (0.6%) 1
    Skin and subcutaneous tissue disorders
    Skin necrosis 1/161 (0.6%) 1
    Vascular disorders
    Deep vein thrombosis 2/161 (1.2%) 2
    Hypotension 1/161 (0.6%) 1
    Orthostatic hypotension 1/161 (0.6%) 1
    Other (Not Including Serious) Adverse Events
    Acalabrutinib + Pembrolizumab
    Affected / at Risk (%) # Events
    Total 157/161 (97.5%)
    Blood and lymphatic system disorders
    Anaemia 35/161 (21.7%) 56
    Febrile neutropenia 4/161 (2.5%) 4
    Increased tendency to bruise 1/161 (0.6%) 2
    Iron deficiency anaemia 1/161 (0.6%) 1
    Leukopenia 3/161 (1.9%) 3
    Lymph node pain 2/161 (1.2%) 2
    Lymphadenopathy 2/161 (1.2%) 2
    Lymphocytosis 1/161 (0.6%) 1
    Methaemoglobinaemia 1/161 (0.6%) 1
    Microcytic anaemia 1/161 (0.6%) 1
    Neutropenia 16/161 (9.9%) 27
    Pancytopenia 1/161 (0.6%) 1
    Polycythaemia 1/161 (0.6%) 1
    Thrombocytopenia 9/161 (5.6%) 20
    Cardiac disorders
    Acute coronary syndrome 1/161 (0.6%) 1
    Angina pectoris 1/161 (0.6%) 1
    Atrial fibrillation 6/161 (3.7%) 9
    Atrial flutter 1/161 (0.6%) 1
    Bradycardia 1/161 (0.6%) 1
    Cardiac failure congestive 1/161 (0.6%) 1
    Cardiomegaly 2/161 (1.2%) 2
    Extrasystoles 1/161 (0.6%) 1
    Myocardial calcification 1/161 (0.6%) 1
    Palpitations 3/161 (1.9%) 3
    Pericardial effusion 3/161 (1.9%) 3
    Pericarditis 1/161 (0.6%) 1
    Sinus tachycardia 5/161 (3.1%) 6
    Supraventricular tachycardia 1/161 (0.6%) 1
    Tachycardia 4/161 (2.5%) 5
    Ventricular tachycardia 1/161 (0.6%) 1
    Ear and labyrinth disorders
    Deafness 1/161 (0.6%) 1
    Deafness neurosensory 1/161 (0.6%) 2
    Ear congestion 3/161 (1.9%) 3
    Ear discomfort 2/161 (1.2%) 2
    Ear haemorrhage 2/161 (1.2%) 2
    Eustachian tube dysfunction 1/161 (0.6%) 1
    Excessive cerumen production 1/161 (0.6%) 1
    Hypoacusis 1/161 (0.6%) 1
    Tinnitus 3/161 (1.9%) 3
    Vertigo 2/161 (1.2%) 2
    Endocrine disorders
    Hyperthyroidism 1/161 (0.6%) 1
    Hypothyroidism 3/161 (1.9%) 3
    Inappropriate antidiuretic hormone secretion 1/161 (0.6%) 1
    Eye disorders
    Borderline glaucoma 1/161 (0.6%) 1
    Cataract 2/161 (1.2%) 2
    Chalazion 1/161 (0.6%) 1
    Conjunctival haemorrhage 2/161 (1.2%) 2
    Dry eye 2/161 (1.2%) 2
    Eye pruritus 1/161 (0.6%) 1
    Eyelid rash 1/161 (0.6%) 1
    Lacrimation increased 1/161 (0.6%) 1
    Macular degeneration 1/161 (0.6%) 1
    Periorbital swelling 2/161 (1.2%) 2
    Vision blurred 6/161 (3.7%) 6
    Vitreous degeneration 1/161 (0.6%) 1
    Gastrointestinal disorders
    Abdominal discomfort 4/161 (2.5%) 4
    Abdominal distension 11/161 (6.8%) 17
    Abdominal pain 13/161 (8.1%) 18
    Abdominal pain lower 2/161 (1.2%) 2
    Abdominal pain upper 10/161 (6.2%) 11
    Anal fistula 1/161 (0.6%) 1
    Anal incontinence 1/161 (0.6%) 1
    Ascites 1/161 (0.6%) 1
    Change of bowel habit 1/161 (0.6%) 1
    Cheilitis 1/161 (0.6%) 1
    Colitis 2/161 (1.2%) 3
    Colitis microscopic 1/161 (0.6%) 1
    Constipation 20/161 (12.4%) 21
    Diarrhoea 73/161 (45.3%) 135
    Dry mouth 6/161 (3.7%) 6
    Duodenal ulcer 1/161 (0.6%) 1
    Dyspepsia 8/161 (5%) 9
    Dysphagia 9/161 (5.6%) 9
    Epigastric discomfort 1/161 (0.6%) 1
    Epiploic appendagitis 1/161 (0.6%) 1
    Flatulence 4/161 (2.5%) 4
    Food poisoning 1/161 (0.6%) 1
    Frequent bowel movements 1/161 (0.6%) 1
    Gastric haemorrhage 1/161 (0.6%) 1
    Gastric ulcer 1/161 (0.6%) 1
    Gastrooesophageal reflux disease 3/161 (1.9%) 3
    Gingival bleeding 1/161 (0.6%) 1
    Gingival discomfort 2/161 (1.2%) 2
    Haematochezia 2/161 (1.2%) 2
    Haemorrhoids 2/161 (1.2%) 2
    Hyperaesthesia teeth 1/161 (0.6%) 1
    Impaired gastric emptying 1/161 (0.6%) 1
    Intestinal perforation 1/161 (0.6%) 1
    Lip swelling 1/161 (0.6%) 1
    Melaena 1/161 (0.6%) 1
    Mouth haemorrhage 1/161 (0.6%) 1
    Mouth ulceration 1/161 (0.6%) 1
    Nausea 43/161 (26.7%) 63
    Oesophageal spasm 1/161 (0.6%) 1
    Oesophageal stenosis 1/161 (0.6%) 1
    Oesophagitis 1/161 (0.6%) 1
    Oral disorder 1/161 (0.6%) 1
    Oral pain 2/161 (1.2%) 3
    Palatal disorder 1/161 (0.6%) 1
    Pancreatitis 1/161 (0.6%) 1
    Paraesthesia oral 1/161 (0.6%) 1
    Proctitis 1/161 (0.6%) 1
    Stomatitis 4/161 (2.5%) 7
    Toothache 1/161 (0.6%) 1
    Vomiting 33/161 (20.5%) 45
    General disorders
    Asthenia 12/161 (7.5%) 13
    Axillary pain 2/161 (1.2%) 2
    Catheter site pain 1/161 (0.6%) 1
    Chest discomfort 2/161 (1.2%) 3
    Chills 13/161 (8.1%) 16
    Drug withdrawal syndrome 1/161 (0.6%) 1
    Early satiety 1/161 (0.6%) 1
    Exercise tolerance decreased 1/161 (0.6%) 1
    Facial pain 1/161 (0.6%) 1
    Fatigue 57/161 (35.4%) 77
    Feeling cold 4/161 (2.5%) 5
    Gait disturbance 4/161 (2.5%) 4
    Influenza like illness 3/161 (1.9%) 3
    Infusion site reaction 1/161 (0.6%) 1
    Malaise 6/161 (3.7%) 6
    Mucosal inflammation 1/161 (0.6%) 1
    Nodule 1/161 (0.6%) 1
    Non-cardiac chest pain 4/161 (2.5%) 5
    Oedema 6/161 (3.7%) 7
    Oedema peripheral 20/161 (12.4%) 24
    Pain 5/161 (3.1%) 7
    Peripheral swelling 1/161 (0.6%) 1
    Polyp 1/161 (0.6%) 1
    Pyrexia 28/161 (17.4%) 40
    Swelling 1/161 (0.6%) 2
    Swelling face 1/161 (0.6%) 2
    Systemic inflammatory response syndrome 2/161 (1.2%) 3
    Thirst 1/161 (0.6%) 1
    Ulcer 1/161 (0.6%) 1
    Hepatobiliary disorders
    Autoimmune hepatitis 3/161 (1.9%) 3
    Immune system disorders
    Allergy to arthropod sting 1/161 (0.6%) 1
    Hypersensitivity 1/161 (0.6%) 1
    Hypogammaglobulinaemia 3/161 (1.9%) 3
    Seasonal allergy 3/161 (1.9%) 3
    Infections and infestations
    Acute sinusitis 2/161 (1.2%) 2
    Bronchitis 9/161 (5.6%) 10
    Candida infection 8/161 (5%) 8
    Cellulitis 2/161 (1.2%) 2
    Clostridium difficile infection 1/161 (0.6%) 1
    Conjunctivitis 3/161 (1.9%) 3
    Cystitis 2/161 (1.2%) 2
    Diverticulitis 1/161 (0.6%) 1
    Ear infection 1/161 (0.6%) 1
    Epiglottitis 1/161 (0.6%) 1
    Escherichia bacteraemia 1/161 (0.6%) 1
    Eye infection 1/161 (0.6%) 1
    Folliculitis 2/161 (1.2%) 2
    Fungal skin infection 1/161 (0.6%) 1
    Gastroenteritis viral 1/161 (0.6%) 1
    Gingival abscess 1/161 (0.6%) 1
    Herpes simplex 1/161 (0.6%) 1
    Herpes zoster 6/161 (3.7%) 8
    Histoplasmosis 1/161 (0.6%) 1
    Histoplasmosis disseminated 1/161 (0.6%) 1
    Infection 1/161 (0.6%) 1
    Influenza 4/161 (2.5%) 5
    Labyrinthitis 1/161 (0.6%) 1
    Localised infection 1/161 (0.6%) 1
    Lower respiratory tract infection 1/161 (0.6%) 1
    Lymphangitis 1/161 (0.6%) 1
    Mucosal infection 1/161 (0.6%) 2
    Nasal herpes 1/161 (0.6%) 1
    Nasopharyngitis 9/161 (5.6%) 12
    Nocardiosis 1/161 (0.6%) 1
    Onychomycosis 1/161 (0.6%) 1
    Oral candidiasis 3/161 (1.9%) 3
    Oral herpes 4/161 (2.5%) 4
    Otitis externa 3/161 (1.9%) 3
    Otitis media 1/161 (0.6%) 1
    Pharyngitis 2/161 (1.2%) 2
    Pharyngitis streptococcal 2/161 (1.2%) 2
    Pneumonia 6/161 (3.7%) 7
    Pneumonia streptococcal 1/161 (0.6%) 1
    Pyuria 1/161 (0.6%) 1
    Rash pustular 2/161 (1.2%) 2
    Respiratory tract infection viral 1/161 (0.6%) 1
    Rhinitis 2/161 (1.2%) 2
    Rhinovirus infection 1/161 (0.6%) 1
    Root canal infection 1/161 (0.6%) 1
    Sepsis 3/161 (1.9%) 3
    Sinusitis 11/161 (6.8%) 13
    Skin infection 1/161 (0.6%) 3
    Soft tissue infection 1/161 (0.6%) 1
    Tooth abscess 1/161 (0.6%) 2
    Upper respiratory tract infection 26/161 (16.1%) 40
    Urinary tract infection 10/161 (6.2%) 13
    Viral infection 1/161 (0.6%) 1
    Vulvovaginal mycotic infection 1/161 (0.6%) 1
    Injury, poisoning and procedural complications
    Animal bite 1/161 (0.6%) 1
    Arthropod bite 3/161 (1.9%) 3
    Arthropod sting 1/161 (0.6%) 1
    Contusion 18/161 (11.2%) 23
    Eye contusion 1/161 (0.6%) 1
    Fall 10/161 (6.2%) 15
    Foreign body 1/161 (0.6%) 1
    Humerus fracture 1/161 (0.6%) 1
    Incision site complication 1/161 (0.6%) 1
    Infusion related reaction 3/161 (1.9%) 4
    Joint injury 1/161 (0.6%) 1
    Ligament sprain 2/161 (1.2%) 2
    Limb injury 1/161 (0.6%) 1
    Lip injury 1/161 (0.6%) 1
    Muscle contusion 2/161 (1.2%) 2
    Muscle strain 1/161 (0.6%) 1
    Periorbital haemorrhage 1/161 (0.6%) 1
    Post procedural diarrhoea 1/161 (0.6%) 1
    Procedural pain 2/161 (1.2%) 2
    Procedural vomiting 1/161 (0.6%) 1
    Rib fracture 1/161 (0.6%) 1
    Skin abrasion 3/161 (1.9%) 3
    Skin injury 1/161 (0.6%) 1
    Vaccination complication 1/161 (0.6%) 2
    Wrist fracture 1/161 (0.6%) 1
    Investigations
    Alanine aminotransferase increased 21/161 (13%) 54
    Amylase increased 1/161 (0.6%) 1
    Aspartate aminotransferase increased 18/161 (11.2%) 29
    Blood alkaline phosphatase increased 3/161 (1.9%) 4
    Blood bilirubin increased 1/161 (0.6%) 1
    Blood creatinine increased 7/161 (4.3%) 11
    Blood immunoglobulin g decreased 1/161 (0.6%) 1
    Blood lactate dehydrogenase increased 2/161 (1.2%) 2
    Blood thyroid stimulating hormone increased 3/161 (1.9%) 3
    Blood uric acid increased 1/161 (0.6%) 1
    Heart rate irregular 1/161 (0.6%) 1
    Immunoglobulins decreased 2/161 (1.2%) 2
    Influenza a virus test positive 1/161 (0.6%) 1
    Lymphocyte count decreased 5/161 (3.1%) 7
    Neutrophil count decreased 4/161 (2.5%) 5
    Oxygen saturation decreased 2/161 (1.2%) 2
    Platelet count decreased 7/161 (4.3%) 11
    Protein total decreased 1/161 (0.6%) 1
    Serum ferritin increased 1/161 (0.6%) 1
    Tri-iodothyronine free decreased 1/161 (0.6%) 1
    Weight decreased 9/161 (5.6%) 11
    Weight increased 2/161 (1.2%) 3
    White blood cell count decreased 4/161 (2.5%) 6
    Metabolism and nutrition disorders
    Cachexia 1/161 (0.6%) 1
    Decreased appetite 42/161 (26.1%) 50
    Dehydration 13/161 (8.1%) 15
    Fluid retention 1/161 (0.6%) 1
    Glucose tolerance impaired 1/161 (0.6%) 1
    Hypercalcaemia 4/161 (2.5%) 7
    Hyperglycaemia 5/161 (3.1%) 7
    Hyperkalaemia 3/161 (1.9%) 3
    Hypernatraemia 1/161 (0.6%) 1
    Hyperphosphataemia 2/161 (1.2%) 2
    Hypertriglyceridaemia 1/161 (0.6%) 1
    Hyperuricaemia 7/161 (4.3%) 9
    Hypoalbuminaemia 3/161 (1.9%) 3
    Hypocalcaemia 4/161 (2.5%) 4
    Hypoglycaemia 2/161 (1.2%) 3
    Hypokalaemia 16/161 (9.9%) 25
    Hypomagnesaemia 10/161 (6.2%) 13
    Hyponatraemia 10/161 (6.2%) 14
    Hypophosphataemia 4/161 (2.5%) 4
    Hypovolaemia 1/161 (0.6%) 2
    Increased appetite 1/161 (0.6%) 1
    Iron deficiency 3/161 (1.9%) 3
    Lactic acidosis 1/161 (0.6%) 1
    Malnutrition 1/161 (0.6%) 1
    Vitamin d deficiency 2/161 (1.2%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/161 (11.8%) 25
    Arthritis 2/161 (1.2%) 2
    Arthropathy 1/161 (0.6%) 1
    Back pain 21/161 (13%) 25
    Bone pain 1/161 (0.6%) 1
    Bursitis 1/161 (0.6%) 1
    Coccydynia 2/161 (1.2%) 2
    Flank pain 8/161 (5%) 8
    Groin pain 3/161 (1.9%) 3
    Joint range of motion decreased 1/161 (0.6%) 1
    Joint stiffness 3/161 (1.9%) 3
    Joint swelling 2/161 (1.2%) 2
    Muscle spasms 13/161 (8.1%) 16
    Muscle tightness 1/161 (0.6%) 1
    Muscular weakness 9/161 (5.6%) 10
    Musculoskeletal chest pain 5/161 (3.1%) 5
    Musculoskeletal pain 8/161 (5%) 11
    Musculoskeletal stiffness 3/161 (1.9%) 3
    Myalgia 12/161 (7.5%) 13
    Neck pain 5/161 (3.1%) 5
    Osteopenia 1/161 (0.6%) 1
    Osteoporosis 2/161 (1.2%) 2
    Pain in extremity 8/161 (5%) 11
    Pain in jaw 1/161 (0.6%) 1
    Synovial cyst 1/161 (0.6%) 1
    Temporomandibular joint syndrome 1/161 (0.6%) 1
    Tendonitis 1/161 (0.6%) 1
    Tenosynovitis 1/161 (0.6%) 1
    Trigger finger 2/161 (1.2%) 2
    Winged scapula 1/161 (0.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acrochordon 1/161 (0.6%) 1
    Basal cell carcinoma 5/161 (3.1%) 5
    Cancer pain 1/161 (0.6%) 1
    Chronic myelomonocytic leukaemia 1/161 (0.6%) 1
    Colon adenoma 1/161 (0.6%) 1
    Lipoma 1/161 (0.6%) 2
    Malignant melanoma 2/161 (1.2%) 3
    Malignant melanoma in situ 1/161 (0.6%) 1
    Melanocytic naevus 2/161 (1.2%) 2
    Prostate cancer recurrent 1/161 (0.6%) 1
    Squamous cell carcinoma 1/161 (0.6%) 1
    Squamous cell carcinoma of skin 1/161 (0.6%) 1
    Tumour compression 1/161 (0.6%) 2
    Tumour pain 2/161 (1.2%) 3
    Nervous system disorders
    Ataxia 1/161 (0.6%) 1
    Dizziness 32/161 (19.9%) 37
    Dizziness postural 2/161 (1.2%) 2
    Dysgeusia 3/161 (1.9%) 4
    Facial paralysis 1/161 (0.6%) 1
    Head discomfort 1/161 (0.6%) 1
    Headache 57/161 (35.4%) 71
    Hypoaesthesia 2/161 (1.2%) 2
    Lethargy 1/161 (0.6%) 1
    Migraine 2/161 (1.2%) 2
    Neuralgia 1/161 (0.6%) 1
    Neuropathy peripheral 10/161 (6.2%) 13
    Paraesthesia 5/161 (3.1%) 5
    Parkinsonism 1/161 (0.6%) 1
    Peripheral motor neuropathy 1/161 (0.6%) 1
    Peripheral sensory neuropathy 3/161 (1.9%) 3
    Presyncope 3/161 (1.9%) 3
    Sciatic nerve neuropathy 1/161 (0.6%) 1
    Sciatica 2/161 (1.2%) 3
    Sinus headache 1/161 (0.6%) 1
    Somnolence 4/161 (2.5%) 4
    Syncope 2/161 (1.2%) 2
    Taste disorder 1/161 (0.6%) 1
    Vocal cord paralysis 1/161 (0.6%) 1
    Psychiatric disorders
    Abnormal dreams 1/161 (0.6%) 1
    Agitation 2/161 (1.2%) 4
    Alcoholism 1/161 (0.6%) 1
    Anxiety 6/161 (3.7%) 6
    Confusional state 7/161 (4.3%) 7
    Delirium 1/161 (0.6%) 1
    Depression 4/161 (2.5%) 4
    Dyssomnia 1/161 (0.6%) 1
    Insomnia 20/161 (12.4%) 21
    Mental status changes 1/161 (0.6%) 1
    Post-traumatic stress disorder 1/161 (0.6%) 1
    Restlessness 1/161 (0.6%) 1
    Sleep disorder 1/161 (0.6%) 1
    Stress 1/161 (0.6%) 1
    Renal and urinary disorders
    Acute kidney injury 5/161 (3.1%) 5
    Bladder spasm 1/161 (0.6%) 1
    Chronic kidney disease 1/161 (0.6%) 1
    Dysuria 5/161 (3.1%) 5
    Haematuria 6/161 (3.7%) 6
    Hypertonic bladder 1/161 (0.6%) 1
    Micturition urgency 1/161 (0.6%) 1
    Nephritis 1/161 (0.6%) 1
    Nocturia 3/161 (1.9%) 3
    Pollakiuria 3/161 (1.9%) 3
    Polyuria 2/161 (1.2%) 2
    Urinary incontinence 2/161 (1.2%) 2
    Urinary retention 3/161 (1.9%) 4
    Urinary tract obstruction 1/161 (0.6%) 1
    Reproductive system and breast disorders
    Atrophic vulvovaginitis 1/161 (0.6%) 1
    Erectile dysfunction 1/161 (0.6%) 1
    Genital lesion 1/161 (0.6%) 1
    Haematospermia 1/161 (0.6%) 1
    Nipple pain 1/161 (0.6%) 1
    Oedema genital 1/161 (0.6%) 1
    Penile pain 1/161 (0.6%) 1
    Prostatitis 1/161 (0.6%) 1
    Vaginal haemorrhage 1/161 (0.6%) 1
    Vulvovaginal pruritus 1/161 (0.6%) 1
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/161 (0.6%) 1
    Bronchial hyperreactivity 1/161 (0.6%) 1
    Bronchial secretion retention 1/161 (0.6%) 1
    Cough 44/161 (27.3%) 68
    Dysphonia 6/161 (3.7%) 6
    Dyspnoea 29/161 (18%) 34
    Dyspnoea exertional 6/161 (3.7%) 7
    Epistaxis 8/161 (5%) 8
    Haemoptysis 1/161 (0.6%) 1
    Hypoxia 1/161 (0.6%) 1
    Laryngeal inflammation 1/161 (0.6%) 1
    Laryngeal oedema 1/161 (0.6%) 1
    Nasal congestion 12/161 (7.5%) 15
    Nasal dryness 1/161 (0.6%) 1
    Oropharyngeal pain 8/161 (5%) 8
    Paranasal sinus discomfort 1/161 (0.6%) 1
    Paranasal sinus hypersecretion 2/161 (1.2%) 2
    Pharyngeal disorder 1/161 (0.6%) 1
    Pharyngeal haemorrhage 1/161 (0.6%) 1
    Pleural effusion 5/161 (3.1%) 5
    Pneumonitis 5/161 (3.1%) 5
    Pneumothorax 1/161 (0.6%) 1
    Productive cough 4/161 (2.5%) 5
    Pulmonary embolism 2/161 (1.2%) 2
    Pulmonary haemorrhage 1/161 (0.6%) 1
    Respiratory failure 1/161 (0.6%) 1
    Respiratory tract congestion 2/161 (1.2%) 2
    Rhinitis allergic 3/161 (1.9%) 4
    Rhinorrhoea 5/161 (3.1%) 6
    Sinus congestion 4/161 (2.5%) 5
    Tachypnoea 1/161 (0.6%) 1
    Throat irritation 1/161 (0.6%) 1
    Tracheal oedema 1/161 (0.6%) 1
    Upper-airway cough syndrome 7/161 (4.3%) 8
    Wheezing 5/161 (3.1%) 5
    Skin and subcutaneous tissue disorders
    Actinic keratosis 2/161 (1.2%) 2
    Alopecia 8/161 (5%) 9
    Angioedema 1/161 (0.6%) 2
    Dandruff 1/161 (0.6%) 2
    Decubitus ulcer 1/161 (0.6%) 1
    Dermatitis 2/161 (1.2%) 2
    Dermatitis contact 3/161 (1.9%) 5
    Drug eruption 1/161 (0.6%) 1
    Dry skin 8/161 (5%) 8
    Ecchymosis 3/161 (1.9%) 3
    Eczema 2/161 (1.2%) 2
    Erythema 5/161 (3.1%) 5
    Erythema multiforme 1/161 (0.6%) 1
    Hyperhidrosis 5/161 (3.1%) 6
    Keloid scar 1/161 (0.6%) 1
    Keratosis pilaris 1/161 (0.6%) 1
    Night sweats 13/161 (8.1%) 14
    Onychoclasis 1/161 (0.6%) 1
    Pain of skin 2/161 (1.2%) 3
    Palmar-plantar erythrodysaesthesia syndrome 1/161 (0.6%) 1
    Papule 1/161 (0.6%) 1
    Petechiae 7/161 (4.3%) 9
    Pruritus 14/161 (8.7%) 15
    Psoriasis 3/161 (1.9%) 3
    Purpura 3/161 (1.9%) 3
    Rash 22/161 (13.7%) 37
    Rash erythematous 4/161 (2.5%) 6
    Rash macular 2/161 (1.2%) 2
    Rash maculo-papular 9/161 (5.6%) 10
    Rash papular 2/161 (1.2%) 2
    Rash pruritic 3/161 (1.9%) 3
    Skin discolouration 1/161 (0.6%) 1
    Skin lesion 5/161 (3.1%) 6
    Skin necrosis 1/161 (0.6%) 1
    Skin plaque 1/161 (0.6%) 1
    Skin sensitisation 2/161 (1.2%) 3
    Skin ulcer 2/161 (1.2%) 4
    Skin ulcer haemorrhage 1/161 (0.6%) 1
    Urticaria papular 1/161 (0.6%) 1
    Vascular disorders
    Aortic stenosis 1/161 (0.6%) 1
    Flushing 1/161 (0.6%) 1
    Haematoma 1/161 (0.6%) 1
    Hot flush 5/161 (3.1%) 5
    Hypertension 8/161 (5%) 10
    Hypotension 21/161 (13%) 23
    Lymphoedema 1/161 (0.6%) 1
    Orthostatic hypotension 2/161 (1.2%) 2
    Pallor 1/161 (0.6%) 1
    Thrombophlebitis superficial 1/161 (0.6%) 1
    Vasculitis 1/161 (0.6%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT 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 Global Clinical Lead
    Organization Acerta Pharma
    Phone 1-877-240-9479
    Email information.center@astrazeneca.com
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT02362035
    Other Study ID Numbers:
    • ACE-LY-005
    First Posted:
    Feb 12, 2015
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jul 1, 2022