Follicular Lymphoma (FL)Phase 1/2KEYNOTE145NCT02362035
ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies
A Phase 1/2 study testing Acalabrutinib and Pembrolizumab in people with Follicular Lymphoma (FL) and CLL, run by Acerta Pharma BV at 19 sites in United States.
Trial summary
This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma (FL), CLL, Small Lymphocytic Lymphoma (SLL)
- What is being tested?
- Acalabrutinib and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 19 sitesUnited States
- Study dates
- 20 Feb 2015to 27 Oct 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Research Site
Boston, Massachusetts, 2215
Research Site
Columbus, Ohio, 43210
Research Site
Dallas, Texas, 75246
Research Site
Denver, Colorado, 80218
Research Site
Fairfax, Virginia, 22031
Research Site
Greenville, South Carolina, 29605
Research Site
Houston, Texas, 77030
Research Site
Los Angeles, California, 90095
Research Site
Nashville, Tennessee, 37203
Research Site
Niles, Illinois, 60714
Research Site
Omaha, Nebraska, 68198-7680
Research Site
Roanoke, Virginia, 24014
Research Site
Rochester, Minnesota, 55905-0001
Research Site
San Antonio, Texas, 78217
Research Site
Tucson, Arizona, 85704
Research Site
Tyler, Texas, 75702
Research Site
Vancouver, Washington, 98684
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Yakima, Washington, 98902
About this study
Official title: A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.
Read the 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).
- Conditions
- Follicular Lymphoma (FL), CLL, Small Lymphocytic Lymphoma (SLL), Richter's Syndrome, Mantle Cell Lymphoma (MCL), Indolent Non Hodgkin Lymphoma
- Being tested
- Acalabrutinib, Pembrolizumab
- 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
- Medical subject headings
- Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Multiple Myeloma, Hodgkin Disease, Burkitt Lymphoma, Leukemia, Hairy Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196
Orally Administered (PO)
PembrolizumabDrug
Also called KEYTRUDA
Intravenous Administered (IV)
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib plus Pembrolizumab | Experimental | 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. Receives: Drug: Acalabrutinib; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 104 weeks
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
Measured: 104 weeks
Number of Participants With Grade 5 Adverse Events
Number of participants with CTCAE Grade 5 (fatal) adverse events
Measured: 104 weeks
Number of Participants With Any Study-Drug Related AE
Study drug-related AEs were those assessed by investigator as related to study treatment.
Measured: 104 weeks
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.
Measured: 104 weeks
Number of Participants With Grade 5 Study-Drug Related AE
Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
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.
Measured: 104 weeks
Number of Participants With AE Leading to Study Drug Delay
An adverse event that caused a temporary withholding of study treatment.
Measured: 104 weeks
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.
Measured: 104 weeks
Secondary outcomes (5)
Overall Response Rate
The percentage of subjects who achieve a partial response or complete response
Measured: 104 weeks
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
Measured: 104 weeks
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
Measured: 104 weeks
Overall Survival
The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause
Measured: 104 weeks
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
Measured: 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2015 (estimated)
- Study start20 Feb 2015
- Primary completion14 Jul 2020
- Study completion27 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Follicular Lymphoma (FL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acerta Pharma BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- AstraZeneca Clinical Study Information Center, Study director, 1-877-240-9479 - information.center@astrazeneca.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02362035
- Sponsor's protocol ID
- ACE-LY-005
- Acronym
- KEYNOTE145
- Status last verified
- Apr 2026
- First submitted
- 7 Feb 2015
- Last updated
- 13 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.