A Study of TAK-981 Given With Rituximab in Adults With Re... | NCT04074330

ID	Type	Description	Link
U1111-1236-0243	Registry Identifier	WHO
2020-003946-36	EudraCT Number

Description Module

Detailed Description

The drug being tested in this study is called TAK-981 in combination with rituximab. The study will include a dose escalation phase (Phase 1) and an expansion phase in select non-Hodgkin lymphoma (NHL) indications (Phase 2).

The study will enroll approximately 180 participants, approximately 35 participants in Phase 1 and approximately 145 participants in Phase 2. The participants with indolent or aggressive relapsed or refractory (r/r) NHL in Phase 1 will identify the maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD). PAD can be defined retrospectively once MTD is reached and it can below MTD or coincide with it. In the dose escalation phase, the starting dose of TAK-981 will be 10 mg. The RP2D will be determined based on the available safety, preliminary pharmacokinetic (PK), pharmacodynamic information data, and after any early antitumor activity observed along with the statistical inference from the Bayesian logistic regression modeling (BLRM).

Participants in the Phase 2 will be enrolled once the Phase 1 of the study is completed, and MTD and/or PAD is determined. Phase 2 will explore the efficacy and safety of TAK-981 in combination with rituximab in participants with select NHL types and indications. Participants in Phase 2 will be enrolled in one of the three treatment arms based on Cohorts:

Phase 2, Cohort A r/r DLBCL Progressed after CAR T-cell therapy:TAK-981+Rituximab
Phase 2, Cohort B:r/r DLBCL;no CAR T-cell Therapy;2-3 Prior Lines: Two Dose Levels of TAK-981+Rituximab
Phase 2, Cohort C:r/r FL;no CAR T-cell Therapy;2-3 Prior Lines: Two Dose Levels of TAK-981+Rituximab

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 72 months. Participants will make multiple visits to the clinic, and will attend the end of treatment (EOT) visit 30 days after receiving their last dose of drug or before the start of subsequent systemic anticancer therapy, whichever occurs first for a follow-up assessment.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1: TAK-981 10mg QW	Experimental	Participants with indolent or aggressive non-Hodgkin lymphoma (NHL) received TAK-981 10 mg, infusion, intravenously (IV), once weekly (QW) on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 milligram per square meter (mg/m^2), infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or disease progression (PD) or unacceptable toxicity.	Drug: TAK-981 Drug: Rituximab
Phase 1: TAK-981 40mg QW	Experimental	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	Drug: TAK-981 Drug: Rituximab
Phase 1: TAK-981 60mg QW	Experimental	Participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	Drug: TAK-981 Drug: Rituximab
Phase 1: TAK-981 90mg QW	Experimental	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
TAK-981	Drug	TAK-981 intravenous infusion.	Phase 1: Japan Lead-in: TAK-981 60mg BIW Phase 1: Japan Lead-in: TAK-981 60mg QW Phase 1: TAK-981 10mg QW

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)	Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug.	From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Phase 1: Number of Participants With Grade 3 or Higher TEAEs	AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.	From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Phase 1: Duration of TEAEs	AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled.

Secondary Outcomes

Measure	Description	Time Frame
Cmax: Maximum Observed Plasma Concentration for TAK-981	As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.	Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Each participant must meet all the following inclusion criteria to be enrolled in the study:

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).
Must be considered ineligible in the opinion of the investigator, or refused autologous stem-cell transplantation (ASCT).
Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (<=) 2.
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).
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.
Left ventricular ejection fraction (LVEF) >=40 percent (%); as measured by echocardiogram or multiple gated acquisition (MUGA) scan.
Suitable venous access for safe drug administration and the study-required PK and pharmacodynamic sampling.
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.
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.
For participants enrolled in Phase 2, if available, mandatory submission of archival tumor tissue acquired ≤12 months prior to screening.
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]).

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

Central nervous system lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan/magnetic resonance imaging (MRI).
History of Grade >=3 infusion-related reaction (IRR) that lead to permanent discontinuation of previous rituximab treatment.
Post transplantation lymphoproliferative disease except relapsed NHL after ASCT.
Undergone ASCT or treatment with cellular therapy including CAR T within <=12 weeks of TAK-981 dosing.
Prior allogeneic hematopoietic stem-cell transplantation.
Lymphomas with leukemic expression.
Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 2 weeks or within at least 5 half-lives before TAK-981 dosing, whichever is shorter. Low dose steroids (oral prednisone or equivalent <=20 mg per day), hormonal therapy for prostate cancer or breast cancer (in adjuvant situation), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are allowed.
Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
Significant medical diseases or conditions, as assessed by the Investigators and sponsor that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to acute myocardial infarction or unstable angina within the last 6 months; uncontrolled diabetes mellitus; significant active bacterial, viral, or fungal infections; severely immunocompromised state; severe non-compensated hypertension and congestive heart failure New York Heart Association Class III or IV; ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary embolism, or symptomatic cerebrovascular events; or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
Known chronic hepatitis C and/or positive serology (unless due to vaccination or passive immunization due to immunoglobulin [Ig] therapy) for chronic hepatitis B. Known Human Immunodeficiency Virus (HIV) infection.
Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.
Receipt of any live vaccine within 4 weeks of initiation of study treatment.
Active, uncontrolled autoimmune disease requiring >20 mg of prednisone or equivalent, cytotoxics or biologicals.
Corticosteroid use within 1 week before the first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Participants requiring steroids at daily doses >20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for lymphoma control or white blood cell count lowering are not eligible.
With baseline prolongation of the QT interval with Fridericia correction method (QTcF) (example, >470 milliseconds (ms) for women and >450 ms for men and a history of congenital long QT syndrome, or torsades de pointes).
Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of Cytochrome P450 3A4/5 (CYP3A4/5) and strong P-glycoprotein (Pgp) inhibitors. To participate in this study, such participants should discontinue use of such agents for at least 2 weeks (1 week for CYP3A4/5 and Pgp inhibitors) before receiving a dose of TAK-981.
Participants in Germany who are committed to an institution by virtue of an order issued either by judicial or administrative authorities as per German law.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
University of Michigan Comprehensive Cancer Center

PubMed Identifier	Type	Citation	Retractions
35226739	Derived	Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.

Label	URL
To obtain more information on the study, click here/on this link	View source

ID	Title	Description
FG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive non-Hodgkin lymphoma (NHL) received TAK-981 10 mg, infusion, intravenously (IV), once weekly (QW) on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 milligram per square meter (mg/m^2), infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or disease progression (PD) or unacceptable toxicity.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 20, 2022	Mar 26, 2024

Arm/Group Information

ID	Title	Description
BG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG002	Phase 1: TAK-981 60mg QW	Participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG003	Phase 1: TAK-981 90mg QW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG004	Phase 1: TAK-981 90mg BIW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG005	Phase 1: TAK-981 120mg QW	Participants with indolent or aggressive NHL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG006	Japan Lead-in: TAK-981 60mg QW	Japanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG007	Japan Lead-in: TAK-981 60mg BIW	Participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle for up to 12 months or PD or unacceptable toxicity.
BG008	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG009	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
BG010	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)

Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG002	Phase 1: TAK-981 60mg QW	Participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG003	Phase 1: TAK-981 90mg QW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG004	Phase 1: TAK-981 90mg BIW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG005	Phase 1: TAK-981 120mg QW	Participants with indolent or aggressive NHL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG006	Japan Lead-in: TAK-981 60mg QW	Japanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG007	Japan Lead-in: TAK-981 60mg BIW	Japanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle for up to 12 months or PD or unacceptable toxicity.

Units	Counts
Participants	OG0003 OG0014 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0014 OG0023 OG003

Primary

Phase 1: Number of Participants With Grade 3 or Higher TEAEs

AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW

Primary

Phase 1: Duration of TEAEs

AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled.

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Median

Full Range

days

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Primary

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level

DLTs were evaluated according to NCI CTCAE, Version 5.0.

The DLT-evaluable analysis set will include participants enrolled in the Phase 1 portion of the study who experienced a DLT at any time after initiation of the first infusion of TAK-981 or who completed all planned infusions of TAK-981 as per schedule plus 3 infusions of rituximab without experiencing a DLT. Overall number of participants analyzed is the number of participants available for analysis.

Posted

Count of Participants

Participants

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Primary

Phase 2: Overall Response Rate (ORR)

ORR was defined as the percentage of participants who achieved complete response (CR) and partial response (PR), as defined by the investigator according to Lugano classification for lymphomas during the study.

Response-evaluable analysis set consisted of participants who have received at least 1 dose of study drug, have sites of measurable disease at Baseline, and 1 postbaseline disease assessment, or were discontinued due to symptomatic deterioration or death before a postbaseline evaluation happens.

Posted

Number

percentage of participants

Up to 42 months

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Cmax: Maximum Observed Plasma Concentration for TAK-981

As per planned analysis, data for this outcome measure were collected and analyzed for the combined population (Phase 1: TAK-981 60mg QW+Japan Lead-in: TAK-981 60mg QW) based on regimen in which same dose groups in Phase 1 irrespective of nationality were pooled. This outcome measure was planned to be analyzed for Phase 1 only.

Pharmacokinetic (PK) analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Overall number of participants analyzed is the number of participants available for analysis. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Mean

Standard Deviation

nanograms per millilitre (ng/ml)

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981

PK analysis set consisted of participants with sufficient dosing and PK data to reliably estimate 1 or more PK parameters. Overall number of participants analyzed is the number of participants available for analysis. Number of participants analyzed is the number of participants available for analysis during the specified time-point.

Posted

Median

Full Range

hours

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981

Posted

Mean

Standard Deviation

hours*ng/mL

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981

Posted

Mean

Standard Deviation

h.ng/ml

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

t1/2z: Terminal Disposition Phase Half-life for TAK-981

Posted

Median

Full Range

hours

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

CL: Total Clearance After Intravenous Administration for TAK-981

Posted

Mean

Standard Deviation

litres per hour (L/h)

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981

Posted

Mean

Standard Deviation

litres (L)

Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieved CR and PR, as defined by the investigator according to Lugano classification for lymphomas during the study.

Posted

Number

percentage of participants

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Disease Control Rate (DCR)

DCR is defined as the percentage of participants who achieved CR, PR, and stable disease (SD) as defined by the investigator according to Lugano classification for Lymphomas during the study.

Posted

Number

percenage of participants

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Duration of Response (DOR)

DOR is the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders (PR or better). DOR was assessed by the investigator according to Lugano classification for lymphoma during the study.

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Time to Progression (TTP)

TTP is defined as the time from the date of first study drug administration to the date of first documented disease progression. TTP was assessed by the investigator according to Lugano classification for lymphoma during the study.

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Progression-Free Survival (PFS)

PFS is defined as the time from the date of the first dose administration to the date of first documentation of PD or death due to any cause, whichever occurs first. PD was determined by Response Evaluation Criteria in Lymphoma. PFS was assessed by the investigator according to Lugano classification for lymphoma during the study.

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Fold Change From Baseline in Levels of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Blood as Assessed by Flow Cytometry During Phase 1

The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in blood. Positive change denotes improvement.

Pharmacodynamic analysis set consisted of participants who have provided evaluable blood samples (C1D1 predose sample and at least 1 postdose sample). Number of participants available is the number of participants with data available for analysis at the specified time point.

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Levels of TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1

The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in skin.

Pharmacodynamic analysis set consisted of participants who have provided evaluable skin biopsies (screening sample and postdose sample). Overall number of participants available is the number of participants available for analysis. Number of participants available is the number of participants with data available for analysis at the specified time point.

Posted

Mean

Standard Deviation

% adduct positive

Cycle 1 Days 1 and 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1

SUMO pathway inhibition in blood was evaluated by flow cytometry with an antibody recognizing SUMO2/3 chains.

Pharmacodynamic analysis set consisted of participants who have provided evaluable blood samples (C1D1 predose sample and at least 1 postdose sample). Overall number of participants analyzed are the number of participants available for analysis. Number of participants available is the number of participants with data available for analysis at the specified time point.

Posted

Mean

Standard Deviation

ratio

Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1

SUMO pathway inhibition in skin was evaluated with skin tissue biopsies by IHC.

Posted

Mean

Standard Deviation

% Sumo 2/3 positive

Cycle 1 Days 1 and 8 (Cycle length = 21 days)

ID	Title	Description
OG000	Phase 1: TAK-981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 1: TAK-981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Number of Participants With Grade 3 or Higher TEAEs

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Count of Participants

Participants

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg

Secondary

Phase 2: Duration of TEAEs

Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.

Posted

Median

Full Range

days

From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Disease Control Rate (DCR)

CR is defined as the percentage of participants who achieved CR, PR, and SD as defined by the investigator according to Lugano classification for Lymphomas during the study.

Posted

Number

percentage of participants

Up to 42 months

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Duration of Response (DOR)

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Time to Progression (TTP)

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Secondary

Phase 2: Progression-Free Survival (PFS)

Posted

Median

Full Range

months

Up to 42 months

ID	Title	Description
OG000	Phase 2 (A): TAK-981 120 mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.
OG001	Phase 2 (C): TAK-981 120 mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1: TAK981 10mg QW	Participants with indolent or aggressive NHL received TAK-981 10 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	0	3	1	3	3	3
EG001	Phase 1: TAK981 40mg QW	Participants with indolent or aggressive NHL received TAK-981 40 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	2	4	2	4	4	4
EG002	Phase 1: TAK981 60mg QW	Participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	0	3	1	3	3	3
EG003	Phase 1: TAK981 90mg QW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	1	7	2	7	6	7
EG004	Phase 1: TAK981 90mg BIW	Participants with indolent or aggressive NHL received TAK-981 90 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	4	8	5	8	8	8
EG005	Phase 1: TAK981 120mg QW	Participants with indolent or aggressive NHL TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	1	6	2	6	6	6
EG006	Japan Lead-in: TAK981 60mg QW	Japanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab 375 mg/m^2, infusion, IV, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	0	1	0	1	1	1
EG007	Japan Lead-in: TAK981 60mg BIW	Japanese participants with indolent or aggressive NHL received TAK-981 60 mg, infusion, IV, BIW on Days 1, 4, 8, and 11 every 21 days in each 21-day treatment cycle for up to 12 months or PD or unacceptable toxicity.	0	3	0	3	3	3
EG008	Phase 2 (A): TAK981 120mg	Participants with r/r DLBCL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	1	2	1	2	2	2
EG009	Phase 2 (C): TAK981 120mg	Participants with FL received TAK-981 120 mg, infusion, IV, QW on Days 1 and 8 every 21 days in each 21-day treatment cycle in combination with rituximab infusion, intravenously, once on Days 1, 8, and 15 of Cycle 1 and then on Day 1 of each 21-day treatment cycle from Cycle 2 for up to 12 months or PD or unacceptable toxicity.	0	1	1	1	1	1

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG0030 affected7 at risk EG0040 affected8 at risk EG0050 affected6 at risk EG0060 affected1 at risk EG0070 affected3 at risk EG0080 affected2 at risk EG0090 affected1 at risk
Atrial flutter	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Cachexia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Death	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
General physical health deterioration	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG0030 affected7 at risk EG0042 affected8 at risk EG0050 affected6 at risk EG0060 affected1 at risk EG0070 affected3 at risk EG0080 affected2 at risk EG0090 affected1 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Amnesia	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0022 affected3 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Atrioventricular block first degree	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Blood creatinine increased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Blood sodium decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
CD4 lymphocytes decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Campylobacter colitis	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Catheter site swelling	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Chest pain	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Chills	General disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Depressed level of consciousness	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Depression	Psychiatric disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dry eye	Eye disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Ear infection	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Electrocardiogram P wave abnormal	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Electrocardiogram ST segment elevation	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Electrocardiogram T wave abnormal	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Eosinophilia	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Extrasystoles	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Eye oedema	Eye disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Eye pruritus	Eye disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Facial pain	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Gait disturbance	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypertension	Vascular disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Infusion site pain	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Infusion site reaction	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Injection site pain	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
International normalised ratio increased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Lentigo	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Malaise	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0002 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Nasal crusting	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0022 affected3 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Oral mucosal blistering	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Otorrhoea	Ear and labyrinth disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pain	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Peripheral swelling	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Phlebitis	Vascular disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Pneumonia	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Prostatomegaly	Reproductive system and breast disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected3 at risk EG003
QRS axis abnormal	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Sinusitis	Infections and infestations	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Somnolence	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Superficial vein thrombosis	Vascular disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Supraventricular extrasystoles	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Testicular oedema	Reproductive system and breast disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Tremor	Nervous system disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Vision blurred	Eye disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25	Systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Weight decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
White blood cell count decreased	Investigations	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Wound haemorrhage	Injury, poisoning and procedural complications	MedDRA 25	Systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003

ID	Term
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins