Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies
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 intravenous (IV)
 administration of XmAb13676 and to determine the maximally tolerated dose (MTD) and/or
 recommended dose (RD).
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 and have relapsed or
 refractory disease

 -  ECOG performance status 0-2

 -  Fertile patients must agree to use highly effective contraception during and for 4
 weeks after last dose of XmAb13676

 -  Able and willing to complete the entire study

 Additional Patient Inclusion Criteria for the DLBCL Cohort (Expansion Phase)

 1. Histologically confirmed diagnosis (specified by 2016 World Health Organization) of
 DLBCL or transformed low-grade lymphoma with measurable disease

 2. Patient must be refractory or have relapsed after 2 or more standard therapeutic
 options, at least one of which must have included anti-CD20 antibody therapy.

 3. Not a candidate for or refusing treatment with hematopoietic stem cell transplantation

 Additional Patient Inclusion Criteria for the Follicular Lymphoma Cohort (Expansion Phase)

 1. Diagnosis of follicular lymphoma Grades 1-3a

 2. Patient must be ineligible for or have exhausted standard therapeutic options and have
 had 2 or more prior systemic regimens.

 Additional Patient Inclusion Criteria for the Mantle Cell Lymphoma Cohort (Expansion Phase)

 1. Diagnosis of mantle cell lymphoma

 2. Patient must be ineligible for or have exhausted standard therapeutic options and have
 had 2 or more prior systemic regimens.

 Additional Patient Inclusion Criteria for the Waldenström Macroglobulinemia Cohort
 (Expansion Phase)

 1. Diagnosis of Waldenström macroglobulinemia

 2. Patient must be ineligible for or have exhausted standard therapeutic options and have
 had 2 or more prior systemic regimens.

 Additional Patient Inclusion Criteria for Richter Transformation Cohort (Expansion Phase)

 1. Diagnosis of Richter transformation Additional Patient Inclusion Criteria for Other
 Indolent Lymphomas Cohort (Expansion Phase)

 1. Diagnosis of other indolent B-cell, non-Hodgkin's lymphomas, specifically the
 following: MALT lymphoma, nodal marginal zone lymphoma, and splenic marginal zone
 lymphoma (NOTE: SLL is not eligible)

 2. Patient must be ineligible for or have exhausted standard therapeutic options and have
 had 2 or more prior systemic regimens.

 Exclusion Criteria:

 -  Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20
 antibodies 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 unless prior diagnosis and documentation of ongoing hemolysis or
 Gilbert's syndrome has been made)

 -  Estimated creatinine clearance < 50 40 mL/min

 -  Active/uncontrolled autoimmune disease

 -  Clinically significant cardiac/cardiovascular disease, or pulmonary compromise

 -  Seizure disorder

 -  History of stroke with the past year6 mos prior to study entry

 -  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

 -  Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening