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

Primary Purpose

Follicular Lymphoma (FL), CLL, Small Lymphocytic Lymphoma (SLL)

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Acalabrutinib
Pembrolizumab
Sponsored by
Acerta Pharma BV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma (FL) focused on measuring Bruton tyrosine kinase inhibitor, Btk, B-Cell Malignancies, Mantle Cell, Multiple Myeloma, CLL, SLL, DLBCL, Follicular, Waldenstrom, Burkitt lymphoma, marginal zone lymphomas, hairy cell leukemia, B cell acute lymphoid leukemia, Acalabrutinib, ACP-196

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 10^9/L or platelet count ≥ 50 x 10^9/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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
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  • Research Site
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  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
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  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acalabrutinib plus Pembrolizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (AEs)
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
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
Number of participants with CTCAE Grade 5 (fatal) adverse events
Number of Participants With Any Study-Drug Related AE
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
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
Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
Number of Participants With Any SAE
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
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
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
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
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
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
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
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
An adverse event that caused a temporary withholding of study treatment.
Number of Participants With AE Leading to Study Drug Modification
An adverse event that resulted in a reduction in the dosage of study treatment for that participant.

Secondary Outcome Measures

Overall Response Rate
The percentage of subjects who achieve a partial response or complete response
Duration of Response
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
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
The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause
Time to Next Treatment
The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment

Full Information

First Posted
February 7, 2015
Last Updated
August 22, 2023
Sponsor
Acerta Pharma BV
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02362035
Brief Title
ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies
Acronym
KEYNOTE145
Official Title
A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 20, 2015 (Actual)
Primary Completion Date
July 14, 2020 (Actual)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acerta Pharma BV
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma (FL), CLL, Small Lymphocytic Lymphoma (SLL), Richter's Syndrome, Mantle Cell Lymphoma (MCL), Indolent Non Hodgkin Lymphoma, Waldenström Macroglobulinemia, Multiple Myeloma, Hodgkin Lymphoma, Burkitt Lymphoma, Marginal Zone Lymphomas, Mediastinal Large B Cell Lymphoma, Hairy Cell Leukemia
Keywords
Bruton tyrosine kinase inhibitor, Btk, B-Cell Malignancies, Mantle Cell, Multiple Myeloma, CLL, SLL, DLBCL, Follicular, Waldenstrom, Burkitt lymphoma, marginal zone lymphomas, hairy cell leukemia, B cell acute lymphoid leukemia, Acalabrutinib, ACP-196

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
161 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acalabrutinib plus Pembrolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
ACP-196
Intervention Description
Orally Administered (PO)
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA
Intervention Description
Intravenous Administered (IV)
Primary Outcome Measure Information:
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
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
Title
Number of Participants With Grade 5 Adverse Events
Description
Number of participants with CTCAE Grade 5 (fatal) adverse events
Time Frame
104 weeks
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
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
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
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
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
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
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
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
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
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
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
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
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
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
The percentage of subjects who achieve a partial response or complete response
Time Frame
104 weeks
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 10^9/L or platelet count ≥ 50 x 10^9/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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AstraZeneca Clinical Study Information Center
Organizational Affiliation
1-877-240-9479 - information.center@astrazeneca.com
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Niles
State/Province
Illinois
ZIP/Postal Code
60714
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
2215
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905-0001
Country
United States
Facility Name
Research Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-7680
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Research Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Research Site
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Facility Name
Research Site
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
Facility Name
Research Site
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ACE-LY-005&amp;attachmentIdentifier=2ded1a27-c5da-4fed-8db9-94e3d52b3efe&amp;fileName=ACE-LY-005_RedactedCSP.pdf&amp;versionIdentifier=
Description
Redacted CSP
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ACE-LY-005&amp;attachmentIdentifier=1f7042f3-d331-4fc2-a94c-958b96d3518e&amp;fileName=ACE-LY-005_RedactedSAP.pdf&amp;versionIdentifier=
Description
Redacted SAP

Learn more about this trial

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

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