KEYNOTE145: ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies
Study Details
Study Description
Brief Summary
This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
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
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:
Drug: Pembrolizumab
Intravenous Administered (IV)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- Number of Participants With Grade 5 Adverse Events [104 weeks]
Number of participants with CTCAE Grade 5 (fatal) adverse events
- 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.
- 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.
- Number of Participants With Grade 5 Study-Drug Related AE [104 weeks]
Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Number of Participants With AE Leading to Study Drug Delay [104 weeks]
An adverse event that caused a temporary withholding of study treatment.
- 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
- Overall Response Rate [104 weeks]
The percentage of subjects who achieve a partial response or complete response
- 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
- 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
- Overall Survival [104 weeks]
The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause
- 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
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.- ACE-LY-005
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
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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
|
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
|
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
|
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
|
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
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 |
information.center@astrazeneca.com |
- ACE-LY-005