Key Eligibility Criteria:

• Provision of signed and dated written informed consent prior to any study specific procedures, sampling, or analyses.

• Age 18 years or older.

• Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following:

Note: For R/R cohorts, patients who have only received 1 line of therapy must be otherwise ineligible for, or intolerant to, available standard-of-care options.

NHL Cohorts:

a. MZL

i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least 1 prior therapy;
ii. Active disease requiring treatment.

b. FL i. R/R follicular lymphoma (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy ii. Active disease requiring treatment.
c. DLBCL

i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy);
ii. Active disease requiring treatment.

d. Transformed indolent B-cell NHL

i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter’s transformation) are not eligible for Part 1;
ii. Active disease requiring treatment MCL Cohorts:

e. WHO-defined MCL

i. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy;
ii. Requiring treatment in the opinion of the investigator.

CLL/SLL Cohorts:

f. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia criteria (Hallek et al 2008):

i. Meeting the following sets of prior treatment criteria:

(1) For R/R cohorts (Cohorts 1B, 1C, 2C, 2D, 2E, 3A, and 4A), disease that relapsed after, or was refractory to, at least 1 prior therapy.
For the venetoclax-treated cohort (Cohort 2E): prior therapy history must include progression after a therapy containing ≥ 2 months of venetoclax treatment (monotherapy or combination).
(2) For the treatment-naïve cohorts (Cohorts 3C and 4B), patients should have no prior treatment for CLL/SLL (other than 1 aborted regimen < 2 weeks in duration and > 4 weeks before enrollment).

Note: TN CLL/SLL patients will only be enrolled at investigational sites where this is allowed by regulatory authorities/local ethics.

ii. Requiring treatment WM Cohorts:

g. WHO-defined WM (clinical and definitive histologic diagnosis)

i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy

ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström’s Macroglobulinemia (Dimopoulos et al 2014)

4. Measurable disease by computed tomography/magnetic resonance imaging, defined as:

a. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes on flow cytometry.
b. DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node > 1.5 cm in longest diameter OR 1 extranodal lesion > 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions. For MZL isolated splenomegaly is considered measurable for this study. For MCL, clonal lymphocytes measured by flow cytometry is considered measurable.
c. WM: serum IgM level > 0.5 g/dL.

Key Exclusion Criteria:

• Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer.

• Underlying medical conditions that, in the investigator’s opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.

• Known central nervous system involvement by lymphoma/leukemia.

• Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter’s syndrome.

• Prior autologous stem cell transplant unless ≥ 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless ≥ 3 months after cell infusion.

• Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent.

• History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.

Eligibility last updated 9/12/22. Questions regarding updates should be directed to the study team contact.