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

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.

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).

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.