A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Acalabrutinib
- Conditions
- Follicular Lymphoma (FL)
- Sponsor
- Acerta Pharma BV
- Enrollment
- 161
- Locations
- 1
- Primary Endpoint
- Number of Participants With Grade 3-4 Adverse Events
- Status
- Completed
- Last Updated
- 4 months ago
Overview
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).
Investigators
Eligibility Criteria
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 ≤
- •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.
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.
Arms & Interventions
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.
Intervention: Acalabrutinib
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Participants With Grade 3-4 Adverse Events
Time Frame: 104 weeks
Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03
Number of Participants With Any Study-Drug Related AE
Time Frame: 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
Time Frame: 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
Time Frame: 104 weeks
Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
Number of Participants With Any Grade 5 Study Drug-Related SAE
Time Frame: 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 Treatment Emergent Adverse Events (AEs)
Time Frame: 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 Any SAE
Time Frame: 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 Any SAE
Time Frame: 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 AE Leading to Study Drug Discontinuation, Modification or Delay
Time Frame: 104 weeks
AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.
Number of Participants With Grade 5 Adverse Events
Time Frame: 104 weeks
Number of participants with CTCAE Grade 5 (fatal) adverse events
Number of Participants With AE Leading to Study Drug Discontinuation
Time Frame: 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
Time Frame: 104 weeks
An adverse event that caused a temporary withholding of study treatment.
Number of Participants With Grade 5 Any SAE
Time Frame: 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
Time Frame: 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 AE Leading to Study Drug Modification
Time Frame: 104 weeks
An adverse event that resulted in a reduction in the dosage of study treatment for that participant.
Number of Participants With Any Grade 3-4 Study Drug-Related SAE
Time Frame: 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.
Secondary Outcomes
- Overall Response Rate(104 weeks)
- Time to Next Treatment(104 weeks)
- Duration of Response(104 weeks)
- Overall Survival(104 weeks)
- Progression-free Survival(104 weeks)