A Study of TAK-981 Given With Rituximab in Adults With Relapsed or Refractory CD20-Positive Non-Hodgkin Lymphoma

Inclusion Criteria

• •1. Participant Population:
• •o. For Phase 1 Dose Escalation: o. aNHL including mantle cell lymphoma and DLBCL histologies such as transformed DLBCL from low-grade lymphoma (follicular or others), DLBCL associated with small-cell infiltration in bone marrow, B-cell lymphoma with intermediate features between DLBCL and Burkitt's lymphoma or with intermediate features between DLBCL and Hodgkin lymphoma, FL grade 3B, and aggressive B-cell lymphoma unclassifiable who must have previously received rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, (Oncovin) and prednisone (R-CHOP) (or equivalent anti-CD20 containing therapy) and 1 additional line of therapy in the r/r setting.
• •o. iNHL (including FL of grades 1-3A and marginal zone lymphoma) refractory to rituximab or to any other anti-CD20 monoclonal antibodies, who have received at least 1 prior systemic therapy for r/r iNHL.
• •o. Rituximab or anti-CD20 refractoriness is defined as failure to respond to, or progression during, any previous rituximab/anti-CD20-containing regimen (monotherapy or combined with chemotherapy), or progression within 6 months of the last rituximab or anti-CD20 dose.
• •Note: The minimum qualifying rituximab/anti-CD20 dose is 1 full cycle (that is, weekly\*4 doses monotherapy or 1 complete dose if combined with chemotherapy). Prior anti-CD20 antibody or cytotoxic drugs may have been administered as single agents or as components of combination therapies. Each repeated course of the same single-agent or combination is considered an independent regimen.
• •o. For Phase 2, the following confirmed CD20+: o. r/r DLBCL progressed or relapsed after a prior CAR T-cells therapy that has received approval by a health authority for the treatment of DLBCL (Cohort A).
• •o. r/r DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not I prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (Cohort B).
• •o. r/r FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least 1 prior line of therapy must have included a CD20-targeted therapy (Cohort C).
• •2. Must be considered ineligible in the opinion of the investigator, or refused autologous stem-cell transplantation (ASCT).
• •3. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\<=) 2.
• •4. Adequate bone marrow function per local laboratory reference range at screening as follows:
• •o Platelet count greater than or equal to (\>=) 75.0\*10\^9/L, Grade 2 thrombocytopenia (platelet count \>=50.0\*10\^9 per liter \[/L\]) is allowed if it is clearly due to marrow involvement with no evidence of myelodysplastic syndrome or hypoplastic bone marrow if found. Absolute neutrophil count (ANC) \>=1.0\*10\^9/L. Hemoglobin \>=85 gram per liter (g/L) (red blood cell \[RBC\] transfusion allowed \>=14 days before assessment).
• •5. Adequate renal and hepatic function, per local laboratory reference range at screening as follows:
• •* Calculated creatinine clearance \>=30 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula.
• •* Potassium levels \>=lower limit of normal (LLN). For potassium \>upper limit of normal (ULN) discussion with Takeda medical monitor (MM)/designee recommended.
• •* Aspartate aminotransferase and alanine aminotransferase \<=3.0\*the ULN of the institution's normal range; bilirubin \<=1.5\*ULN. Participants with Gilbert's syndrome may have a bilirubin level \>1.5\*ULN, per discussion between the investigator and the medical monitor.
• •6. Left ventricular ejection fraction (LVEF) \>=40 percent (%); as measured by echocardiogram or multiple gated acquisition (MUGA) scan.
• •7. Suitable venous access for safe drug administration and the study-required PK and pharmacodynamic sampling.
• •8. Have at least 1 bidimensionally measurable lesion per Lugano Classification by computed tomography (CT). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• •9. Willing to consent to 1 mandatory pretreatment and 1 on-treatment skin biopsy during Phase 1. The skin biopsy entry requirement may be discontinued by the sponsor once there is enough pharmacodynamic evidence of target engagement.
• •10. For participants enrolled in Phase 2, if available, mandatory submission of archival tumor tissue acquired ≤12 months prior to screening.
• •11. Recovered to Grade 1, baseline or established as sequela, from all toxic effects of previous therapy (except alopecia, neuropathy, autoimmune endocrinopathies with stable endocrine replacement therapy, neurotoxicity \[Grade 1 or 2 permitted\], or bone marrow parameters \[any of Grade 1, 2, permitted if directly related to bone marrow involvement\]).