Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies

The purpose of this study is to determine the safety and tolerability of weekly intravenous (IV) administration of XmAb13676 and to determine the maximally tolerated dose (MTD) after the first dose, and then to determine the MTD after second and subsequent infusions.

Inclusion Criteria

• Able to provide written informed consent
• Diagnosis of either Non-CLL B cell malignancy or CLL/SLL
• Ineligible for or have exhausted standard therapeutic options
• Last dose of anti-CD20 antibody therapy must have been >4 weeks before the first dose of XmAb13676
• ECOG performance status 0-2
• Not a candidate for or refusing treatment with hematopoietic stem cell transplantation
• Fertile patients must agree to use effective contraception during and for 4 weeks after completion of study
• Able and willing to complete the entire study

Exclusion Criteria

• Cytotoxic chemotherapy, radiotherapy, or immunotherapy within 4 weeks, or small molecule or investigational agents within 6 elimination half-lives of the first dose of XmAb13676
• Prior allogeneic stem cell or solid organ transplantation
• Failure to recover from Grade 3 or 4 toxicity from previous treatment
• Multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia
• Known intolerance to CD20 monoclonal antibody therapy
• History of primary central nervous system lymphoma or neoplastic central nervous system disease
• Platelet count < 50 x 10^9/L
• Absolute neutrophil count < 1.0 x 10^9/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at screening > 3x upper limit of normal (ULN)
• Bilirubin > 1.5 mg/dL
• Estimated creatinine clearance < 50 mL/min
• Active/uncontrolled autoimmune disease
• Clinically significant cardiac/cardiovascular disease, or pulmonary compromise
• Seizure disorder
• History of stroke with the past year
• History or evidence of a clinically unstable/uncontrollable disorder, condition or disease other than primary malignancy, that in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures or completion
• Evidence of any serious bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to study entry
• Positive test for human immunodeficiency virus (HIV) or hepatitis C (HCV) antibodies (unless HCV viral load test by PCR is negative)
• Positive test for HbsAg, or positive test for HBcAb (unless serology is positive due to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if HBsAb is present.
• Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the End of Study visit

Lead Organization
Xencor, Inc.

Primary ID XmAb13676-01
Secondary IDs NCI-2016-01843
Clinicaltrials.gov ID NCT02924402