TerminatedNCT04074330Updated Jun 14, 2024Results posted

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

A Phase 1/2 interventional study of TAK-981 and Rituximab in Lymphoma, Non-Hodgkin, sponsored by Takeda. Terminated at 59 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-14.

Sponsored by Takeda · Phase 1/2, Interventional, and Treatment

Why this study was terminated

Enrolment Challenges

Phase: Phase 1/2
Study type: Interventional
Enrollment: 38
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

This study is about a medicine called TAK-981 given with rituximab, used to treat adults with relapsed or refractory CD20-positive non-Hodgkin lymphoma.

This study has 2 parts.

The main aims of the study are:

To check for side effects from treatment with TAK-981 given with rituximab.
To check how much TAK-981 participants can tolerate.
To check if participants with diffuse large B-cell lymphoma or follicular lymphoma respond well to treatment.

Participants will receive TAK-981 and rituximab in 21-day cycles. They will continue treatment for about 12 months unless their condition gets worse (disease progression), they cannot tolerate the treatment, or they leave the study for certain reasons.

Read the 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.

Conditions studied

Lymphoma, Non-Hodgkin

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Keywords

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In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 38 is close to the median of 40 across 4,508 interventional studies indexed under Lymphoma.

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Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 38 participants (actual)

Study arms

Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
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.
Drug: TAK-981 · Drug: Rituximab
Experimental
Phase 1: 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.
Drug: TAK-981 · Drug: Rituximab
Experimental
Phase 1: 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.
Drug: TAK-981
Experimental
Phase 2 (A): TAK-981 120 mg
Participants with relapsed or refractory (r/r) diffuse large B-cell lymphoma (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.
Drug: TAK-981 · Drug: Rituximab
Experimental
Phase 2 (C): TAK-981 120 mg
Participants with follicular lymphoma (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.
Drug: TAK-981 · Drug: Rituximab

Interventions

DrugTAK-981
TAK-981 intravenous infusion.
DrugRituximab
Rituximab intravenous infusion.

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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 Dose Limiting Toxicities (DLTs) Per Dose Level
DLTs were evaluated according to NCI CTCAE, Version 5.0.
Time frame: Up to 42 months
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.
Time frame: Up to 42 months

Secondary outcomes

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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
t1/2z: Terminal Disposition Phase Half-life 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
CL: Total Clearance After Intravenous Administration 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Vss: Volume of Distribution at Steady State After Intravenous Administration 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.
Time frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
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.
Time frame: Up to 42 months
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.
Time frame: Up to 42 months
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.
Time frame: Up to 42 months
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.
Time frame: Up to 42 months
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.
Time frame: Up to 42 months
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.
Time frame: 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)
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.
Time frame: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
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.
Time frame: 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)
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.
Time frame: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
Phase 2: 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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Phase 2: 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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Phase 2: 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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
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.
Time frame: Up to 42 months
Phase 2: 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.
Time frame: Up to 42 months
Phase 2: 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.
Time frame: Up to 42 months
Phase 2: 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.
Time frame: Up to 42 months

Results

Posted Jun 14, 2024

Limitations and caveats

The study was terminated due to enrollment challenges.

Participant flow

Participants took part in the study at 12 investigative sites in the United States, Canada, and Japan from 15 October 2019 to 26 April 2023.

Dose Escalation (up to 19.36 Months)

Participant flow — Dose Escalation (up to 19.36 Months)
Milestone	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Started	3	4	3	7	8	6	1	3
Completed	0	0	0	0	0	0	0	0
Not completed	3	4	3	7	8	6	1	3
Withdrew: Death	0	2	0	1	4	1	0	0
Withdrew: Progressive disease	2	0	0	5	2	2	1	2
Withdrew: Start of new systemic treatment	0	0	1	0	0	0	0	0
Withdrew: Site terminated by sponsor	0	0	0	0	0	1	0	1
Withdrew: Withdrawal by subject	1	1	1	0	2	1	0	0
Withdrew: Reason not specified	0	1	1	1	0	1	0	0

Dose Expansion (up to 42 Months)

Participant flow — Dose Expansion (up to 42 Months)
Milestone	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Started	2	1
Completed	0	0
Not completed	2	1
Withdrew: Death	1	0
Withdrew: Study terminated by sponsor	1	1

Outcome measures

PrimaryPhase 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.

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)
Participants	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)	3	4	3	6	8	6	1	3

PrimaryPhase 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.

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With Grade 3 or Higher TEAEs
Participants	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Number of Participants With Grade 3 or Higher TEAEs	1	4	1	2	7	3	1	2

PrimaryPhase 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.

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Median · days

Phase 1: Duration of TEAEs
days	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Duration of TEAEs	57.0 (1 to 775)	8.0 (1 to 575)	13.0 (1 to 473)	2.0 (1 to 360)	11.0 (1 to 274)	10.0 (1 to 838)	2.0 (1 to 657)

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

DLTs were evaluated according to NCI CTCAE, Version 5.0.

Time frame:: Up to 42 months
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level
Participants	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level	0	0	0	0	0	0	0	0

PrimaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Number · percentage of participants

Phase 2: Overall Response Rate (ORR)
percentage of participants	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Overall Response Rate (ORR)	50	100

SecondaryCmax: 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.

Time frame:: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Reported as:: Mean · nanograms per millilitre (ng/ml)

Cmax: Maximum Observed Plasma Concentration for TAK-981
nanograms per millilitre (ng/ml)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	39.8 ± 19.1	184 ± 139	444 ± 323	648 ± 214	810 ± 305	740 ± 491	833 ± 73.3
Cycle 1 Day 8	51.4 ± 13.9	200 ± 152	595 ± 410	600 ± 146	967 ± 299	981 ± 272	731 ± 346

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

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

Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981
hours	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	1.17 (1.15 to 1.20)	1.15 (1.14 to 1.42)	1.14 (0.97 to 1.29)	1.14 (1.09 to 1.39)	1.17 (1.07 to 1.53)	1.28 (1.10 to 1.95)	1.12 (1.12 to 1.48)
Cycle 1 Day 8	1.15 (1.07 to 1.24)	1.08 (1.04 to 1.27)	0.95 (0.93 to 1.02)	1.08 (1.02 to 1.72)	1.05 (1.00 to 1.30)	1.11 (1.05 to 1.19)	1.12 (1.04 to 1.67)

SecondaryAUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981

Time frame:: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Reported as:: Mean · hours*ng/mL

AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981
hours*ng/mL	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	146 ± 15.0	477 ± 130	1070 ± 456	1310 ± 380	1490 ± 475	1640 ± 484	1520 ± 103
Cycle 1 Day 8	140 ± 25.6	517 ± 236	1160 ± 510	1290 ± 351	1640 ± 483	1780 ± 333	1420 ± 356

SecondaryAUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981

Time frame:: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Reported as:: Mean · h.ng/ml

AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981
h.ng/ml	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	151 ± 15.1	498 ± 128	1110 ± 465	1360 ± 398	1640 ± 445	1600 ± 550	1560 ± 114
Cycle 1 Day 8	150 ± 19.2	538 ± 242	1210 ± 514	1330 ± 359	1780 ± 490	1830 ± 344	1460 ± 382

Secondaryt1/2z: Terminal Disposition Phase Half-life for TAK-981

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

t1/2z: Terminal Disposition Phase Half-life for TAK-981
hours	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	5.06 (4.78 to 5.41)	5.88 (5.31 to 6.76)	6.02 (5.67 to 6.46)	5.75 (4.50 to 7.01)	4.88 (4.21 to 7.23)	5.78 (2.87 to 8.35)	5.91 (5.12 to 6.00)
Cycle 1 Day 8	5.03 (3.15 to 5.92)	5.92 (5.51 to 6.15)	5.77 (5.12 to 7.14)	5.78 (4.98 to 6.29)	5.59 (3.10 to 10.93)	5.73 (5.23 to 6.46)	5.45 (4.16 to 6.91)

SecondaryCL: Total Clearance After Intravenous Administration for TAK-981

Time frame:: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Reported as:: Mean · litres per hour (L/h)

CL: Total Clearance After Intravenous Administration for TAK-981
litres per hour (L/h)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	66.8 ± 6.37	83.8 ± 17.8	65.2 ± 37.0	72.7 ± 27.2	58.2 ± 15.5	81.8 ± 24.7	38.6 ± 2.78
Cycle 1 Day 8	67.4 ± 8.23	75.2 ± 43.8	57.8 ± 26.2	73.3 ± 25.9	53.9 ± 14.6	68.0 ± 16.1	43.2 ± 13.1

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

Time frame:: Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days)
Reported as:: Mean · litres (L)

Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
litres (L)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1 + Japan Lead-in: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1	396 ± 72.8	517 ± 202	406 ± 277	352 ± 136	255 ± 75.5	410 ± 156	154 ± 1.72
Cycle 1 Day 8	352 ± 79.9	456 ± 278	332 ± 211	347 ± 110	273 ± 201	307 ± 95.0	189 ± 68.0

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Number · percentage of participants

Phase 1: Overall Response Rate (ORR)
percentage of participants	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Overall Response Rate (ORR)	33.3	50.0	66.7	14.3	0	33.3	0	33.3

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Number · percenage of participants

Phase 1: Disease Control Rate (DCR)
percenage of participants	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Disease Control Rate (DCR)	100	50.0	100	28.6	16.7	50.0	0	33.3

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 1: Duration of Response (DOR)
months	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Duration of Response (DOR)	8.31 (8.31 to 8.31)	—	—	2.73 (2.73 to 2.73)	—	—	—	8.94 (8.94 to 8.94)

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 1: Time to Progression (TTP)
months	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Time to Progression (TTP)	12.42 (2.69 to 12.42)	—	—	1.58 (0.95 to 3.98)	1.48 (0.00 to 3.91)	NA (0.92 to 19.09)	—	13.18 (13.18 to 13.18)

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 1: Progression-Free Survival (PFS)
months	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Phase 1: Progression-Free Survival (PFS)	12.42 (2.69 to 12.42)	—	—	1.58 (1.25 to 3.98)	2.33 (0.43 to 3.91)	NA (1.61 to 19.09)	—	13.18 (13.18 to 13.18)

SecondaryPhase 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.

Time frame:: 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)
Reported as:: Mean · ratio

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
ratio	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1 /1 Hour Postdose	4.1 ± 0.54	5.7 ± 1.47	6.3 ± 1.02	9.5 ± 1.04	7.6 ± 0.73	9.9 ± 2.84	4.9 ± NA	6.7 ± 1.42
Cycle 1 Day 1 /4 Hours Postdose	3.6 ± 0.66	4.7 ± 1.18	4.7 ± 1.28	6.7 ± 1.07	4.9 ± 1.69	6.5 ± 0.56	—	4.1 ± NA
Cycle 1 Day 1 /8 Hours Postdose	3.7 ± 0.27	4.5 ± 1.22	4.1 ± 1.24	5.6 ± 1.05	4.6 ± 0.72	5.2 ± 0.64	3.0 ± NA	3.3 ± 0.32
Cycle 1 Day 8 /Predose	1.8 ± 0.13	1.9 ± 0.68	1.9 ± 0.27	2.5 ± 0.88	2.8 ± 0.51	2.8 ± 1.50	1.1 ± NA	1.6 ± 0.17
Cycle 1 Day 8 /1 Hour Postdose	4.6 ± 0.19	6.6 ± 0.96	8.0 ± 0.87	9.1 ± 3.21	7.8 ± 0.61	11.6 ± 6.34	5.0 ± NA	5.4 ± 0.69
Cycle 1 Day 8 /4 Hours Postdose	3.9 ± 0.19	6.2 ± 1.87	5.1 ± 0.70	6.1 ± 2.16	5.8 ± 0.65	5.6 ± 1.73	—	4.3 ± NA
Cycle 1 Day 8 /8 Hours Postdose	3.2 ± 0.55	4.2 ± 1.34	4.0 ± 0.49	5.3 ± 1.97	4.0 ± 1.43	7.1 ± 2.83	2.9 ± NA	3.3 ± 0.38

SecondaryPhase 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.

Time frame:: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
Reported as:: Mean · % adduct positive

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
% adduct positive	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1 /Predose	0.0 ± 0.03	0.0 ± 0.0	0.0 ± 0.0	0.0 ± 0.0	—	0.0 ± 0.0	0.0 ± NA	0.0 ± 0.0
Cycle 1 Day 8	1.2 ± 1.15	15.8 ± 12.70	27.0 ± 12.29	22.6 ± 9.47	59.7 ± NA	11.2 ± 11.35	1.4 ± NA	29.5 ± 19.88

SecondaryPhase 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.

Time frame:: 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)
Reported as:: Mean · ratio

Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1
ratio	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1 /1 Hour Postdose	0.9 ± 0.05	0.8 ± 0.15	0.5 ± 0.36	0.6 ± 0.11	0.5 ± 0.26	0.6 ± 0.22	0.1 ± NA	0.8 ± 0.33
Cycle 1 Day 1 /4 Hours Postdose	0.9 ± 0.07	0.8 ± 0.15	0.5 ± 0.34	0.5 ± 0.15	0.4 ± 0.30	0.9 ± 0.14	—	1.0 ± NA
Cycle 1 Day 1 /8 Hours Postdose	1.0 ± 0.05	0.8 ± 0.17	0.5 ± 0.33	0.5 ± 0.15	0.5 ± 0.22	0.7 ± 0.28	0.2 ± NA	0.8 ± 0.24
Cycle 1 Day 8 /Predose	0.9 ± 0.09	1.1 ± 0.37	0.8 ± 0.12	1.1 ± 0.46	0.9 ± 0.07	1.1 ± 0.25	0.2 ± NA	0.7 ± 0.33
Cycle 1 Day 8 /1 Hour Postdose	0.9 ± 0.10	0.8 ± 0.34	0.5 ± 0.19	0.5 ± 0.05	0.5 ± 0.14	0.6 ± 0.10	0.1 ± NA	0.5 ± 0.25
Cycle 1 Day 8 /4 Hours Postdose	0.9 ± 0.09	0.7 ± 0.31	0.5 ± 0.23	0.6 ± 0.20	0.7 ± 0.05	0.7 ± 0.10	—	1.2 ± NA
Cycle 1 Day 8 /8 Hours Postdose	0.9 ± 0.09	0.7 ± 0.37	0.5 ± 0.04	0.5 ± 0.13	0.5 ± 0.35	0.7 ± 0.17	0.2 ± NA	0.7 ± 0.31

SecondaryPhase 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.

Time frame:: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
Reported as:: Mean · % Sumo 2/3 positive

Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1
% Sumo 2/3 positive	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW
Cycle 1 Day 1 /Predose	83.40383 ± 2.692876	87.74383 ± 5.142812	89.60727 ± 5.528530	89.63755 ± 4.044536	—	75.79235 ± 2.586486	86.85370 ± NA	69.65077 ± 19.035919
Cycle 1 Day 8	82.26130 ± 2.017705	79.34405 ± 10.262143	55.69903 ± 19.325964	52.54200 ± 15.606775	51.84200 ± NA	63.14625 ± 15.415286	69.68880 ± NA	41.79763 ± 21.796849

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

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Count of participants · Participants

Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)
Participants	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)	2	1

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

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Count of participants · Participants

Phase 2: Number of Participants With Grade 3 or Higher TEAEs
Participants	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Number of Participants With Grade 3 or Higher TEAEs	2	1

SecondaryPhase 2: Duration of TEAEs

Time frame:: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Reported as:: Median · days

Phase 2: Duration of TEAEs
days	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Duration of TEAEs	8.0 (1 to 483)	2.0 (1 to 349)

SecondaryPhase 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.

Time frame:: Up to 42 months
Reported as:: Number · percentage of participants

Phase 2: Disease Control Rate (DCR)
percentage of participants	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Disease Control Rate (DCR)	1	1

SecondaryPhase 2: Duration of Response (DOR)

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 2: Duration of Response (DOR)
months	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Duration of Response (DOR)	3.32 (3.32 to 3.32)	0.03 (0.03 to 0.03)

SecondaryPhase 2: Time to Progression (TTP)

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 2: Time to Progression (TTP)
months	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Time to Progression (TTP)	5.32 (5.32 to 5.32)	1.48 (1.48 to 1.48)

SecondaryPhase 2: Progression-Free Survival (PFS)

Time frame:: Up to 42 months
Reported as:: Median · months

Phase 2: Progression-Free Survival (PFS)
months	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg
Phase 2: Progression-Free Survival (PFS)	3.15 (1.0 to 5.3)	1.48 (1.48 to 1.48)

Adverse events

Collected over From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1: TAK981 10mg QW	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Phase 1: TAK981 40mg QW	2/4 (50%)	2/4 (50%)	4/4 (100%)
Phase 1: TAK981 60mg QW	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Phase 1: TAK981 90mg QW	1/7 (14.3%)	2/7 (28.6%)	6/7 (85.7%)
Phase 1: TAK981 90mg BIW	4/8 (50%)	5/8 (62.5%)	8/8 (100%)
Phase 1: TAK981 120mg QW	1/6 (16.7%)	2/6 (33.3%)	6/6 (100%)
Japan Lead-in: TAK981 60mg QW	0/1 (0%)	0/1 (0%)	1/1 (100%)
Japan Lead-in: TAK981 60mg BIW	0/3 (0%)	0/3 (0%)	3/3 (100%)
Phase 2 (A): TAK981 120mg	1/2 (50%)	1/2 (50%)	2/2 (100%)
Phase 2 (C): TAK981 120mg	0/1 (0%)	1/1 (100%)	1/1 (100%)

Most frequent serious events

Showing 10 of 21

Most frequent serious events
Event	Phase 1: TAK981 10mg QW	Phase 1: TAK981 40mg QW	Phase 1: TAK981 60mg QW	Phase 1: TAK981 90mg QW	Phase 1: TAK981 90mg BIW	Phase 1: TAK981 120mg QW	Japan Lead-in: TAK981 60mg QW	Japan Lead-in: TAK981 60mg BIW	Phase 2 (A): TAK981 120mg	Phase 2 (C): TAK981 120mg
Cytokine release syndromeImmune system disorders	0/3	0/4	0/3	0/7	0/8	1/6	0/1	0/3	0/2	1/1
LymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	0/4	0/3	0/7	0/8	0/6	0/1	0/3	1/2	0/1
Abdominal painGastrointestinal disorders	1/3	0/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
COVID-19 pneumoniaInfections and infestations	0/3	0/4	1/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
Atrial flutterCardiac disorders	0/3	1/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
Back painMusculoskeletal and connective tissue disorders	0/3	1/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
DeathGeneral disorders	0/3	1/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
Diffuse large B-cell lymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	0/4	0/3	0/7	2/8	0/6	0/1	0/3	0/2	0/1
Large intestine perforationGastrointestinal disorders	0/3	1/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	1/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	0/1

Most frequent other events

Showing 10 of 156

Most frequent other events
Event	Phase 1: TAK981 10mg QW	Phase 1: TAK981 40mg QW	Phase 1: TAK981 60mg QW	Phase 1: TAK981 90mg QW	Phase 1: TAK981 90mg BIW	Phase 1: TAK981 120mg QW	Japan Lead-in: TAK981 60mg QW	Japan Lead-in: TAK981 60mg BIW	Phase 2 (A): TAK981 120mg	Phase 2 (C): TAK981 120mg
Alanine aminotransferase increasedInvestigations	0/3	0/4	0/3	0/7	0/8	0/6	1/1	0/3	0/2	0/1
Aspartate aminotransferase increasedInvestigations	0/3	0/4	0/3	0/7	0/8	0/6	1/1	0/3	0/2	0/1
ChillsGeneral disorders	1/3	0/4	0/3	3/7	3/8	5/6	0/1	0/3	2/2	0/1
ConstipationGastrointestinal disorders	0/3	1/4	1/3	1/7	1/8	2/6	0/1	0/3	1/2	1/1
Dermatitis bullousSkin and subcutaneous tissue disorders	0/3	0/4	0/3	0/7	0/8	0/6	1/1	0/3	0/2	0/1
Ejection fraction decreasedInvestigations	0/3	0/4	0/3	1/7	0/8	0/6	0/1	0/3	0/2	1/1
Electrocardiogram ST segment elevationInvestigations	0/3	0/4	0/3	0/7	0/8	0/6	0/1	0/3	0/2	1/1
EosinophiliaBlood and lymphatic system disorders	0/3	0/4	0/3	0/7	0/8	0/6	1/1	0/3	0/2	0/1
Facial painGeneral disorders	0/3	0/4	0/3	0/7	0/8	0/6	1/1	0/3	0/2	0/1
FatigueGeneral disorders	2/3	1/4	0/3	1/7	2/8	5/6	0/1	0/3	0/2	1/1

Baseline characteristics

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

Age, Continuous
Age, Continuous(years)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg	Total
Mean	64.0 (56.0 to 77.0)	69.3 (60.0 to 80.0)	73.0 (67.0 to 79.0)	57.7 (29.0 to 65.0)	64.8 (46.0 to 78.0)	58.8 (35.0 to 79.0)	61.0 (61.0 to 61.0)	70.3 (68.0 to 72.0)	71 (67 to 75)	55 (55 to 55)	64.5 (29.0 to 80.0)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg	Total
Female	1	1	1	2	2	1	1	3	0	0	12
Male	2	3	2	5	6	5	0	0	2	1	26

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg	Total
Hispanic or Latino	0	0	0	0	0	0	0	0	0	0	0
Not Hispanic or Latino	3	4	2	7	7	6	1	3	2	1	36
Unknown or Not Reported	0	0	1	0	1	0	0	0	0	0	2

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase 1: TAK-981 10mg QW	Phase 1: TAK-981 40mg QW	Phase 1: TAK-981 60mg QW	Phase 1: TAK-981 90mg QW	Phase 1: TAK-981 90mg BIW	Phase 1: TAK-981 120mg QW	Japan Lead-in: TAK-981 60mg QW	Japan Lead-in: TAK-981 60mg BIW	Phase 2 (A): TAK-981 120 mg	Phase 2 (C): TAK-981 120 mg	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0
Asian	0	1	0	0	0	0	1	3	0	0	5
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	1	0	0	0	0	0	1
White	3	3	3	7	6	6	0	0	2	1	31
More than one race	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	1	0	0	0	0	0	1

Study locations

59 sites

University of Alabama at Birmingham
Birmingham, Alabama 35294, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109, United States
Mayo Clinic - Cancer Center - Rochester - PPDS
Rochester, Minnesota 55905, United States
Levine Cancer Institute - Charlotte
Chapel Hill, North Carolina 27514, United States
East Carolina University
Greenville, North Carolina 27834, United States
University of Cincinnati
Cincinnati, Ohio 45219, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106, United States
Ohio State University Wexner Medical Center
Columbus, Ohio 43210, United States
City of Hope - Comprehensive Cancer Center (CCC)
Portland, Oregon 97239, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania 15224, United States
Texas Oncology (Medical City) - USOR
Dallas, Texas 75230, United States
Texas Oncology (Tyler) - USOR
Tyler, Texas 75702, United States
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec H2L 4M1, Canada
Sir Mortimer B Davis Jewish General Hospital
Pointe-Claire, Quebec H9R 4S3, Canada
Beijing Cancer Hospital
Beijing, Beijing 100142, China
Shanghai East Hospital
Shanghai, Shanghai 200123, China
Institut Paoli Calmettes
Marseille, Bouches-du-Rhone 13273, France
Hopital Francois Mitterand
Dijon, Cote-d'Or 21000, France
CHU Montpellier - Hopital St Eloi
Montpellier, Herault 34090, France
Hopital Prive Sevigne
Rennes, Ille-et-Vilaine 35000, France
Hotel Dieu - Nantes
Nantes, Loire-Atlantique 44093, France
Centre Henri Becquerel
Rouen, Seine-Maritime 76038, France
Hopital Saint Antoine
Paris, 75012, France
Hopital Universitaire Pitie Salpetriere
Paris, 75013, France
Universitatsklinikum Freiburg
Freiburg, Baden-Wurttemberg 79106, Germany
Universitatsklinikum Tubingen
Tubingen, Baden-Wurttemberg 72076, Germany
Klinikum rechts der Isa der Technischen Universitaet Muenchen
Munchen, Bayern 81675, Germany
Universitatsklinikum Wurzburg
Wurzburg, Bayern 97080, Germany
Universitatsklinikum Essen
Essen, Nordrhein-Westfalen 45147, Germany
Otto-von-Guericke-Universitat Magdeburg
Magdeburg, Sachsen-Anhalt 39120, Germany
Universitatsklinikum Leipzig
Leipzig, Sachsen 04103, Germany
Charite - Universitatsmedizin Berlin
Berlin, 12203, Germany
Azienda Sanitaria Locale di Ravenna
Ravenna, Emilia-Romagna 48100, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Lazio 00152, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Milano, Lombardia 20122, Italy
Istituto Nazionale Dei Tumori
Milano, Lombardia 20133, Italy
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
Milano, Lombardia 20162, Italy
A.O.U. Maggiore della Carita
Novara, Piemonte 28100, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, Piemonte 10126, Italy
Azienda Ospedaliera Cardinale G Panico
Tricase, Puglia 73039, Italy
Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia, 27100, Italy
National Hospital Organization Nagoya Medical Center
Nagoya-Shi, Aiti 460-0001, Japan
National University Corporation Tohoku University Tohoku University Hospital
Sendai-Shi, Miyagi 980-0872, Japan
Kindai University Hospital
Osakasayama-Shi, Osaka 589-0014, Japan
National Cancer Center Hospital East
Kashiwa, Tiba 277-8577, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Koto-Ku, Tokyo 135-0063, Japan
Hospital Clinic de Barcelona
Barcelona, '08036, Spain
Hospital del Mar
Barcelona, 08003, Spain
Hospital de La Santa Creu i Sant Pau
Barcelona, 08041, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario La Paz - PPDS
Madrid, 28046, Spain
Complejo Asistencial Universitario de Salamanca H. Clinico
Salamanca, 37007, Spain
Hospital Universitario Virgen del Rocio - PPDS
Sevilla, 41013, Spain
Derriford Hospital
Plymouth, Devon PL6 8DH, United Kingdom
Beatson West of Scotland Cancer Centre - PPDS
Glasgow, Lanarkshire G12 0YN, United Kingdom
University College London
London, London, City Of NW1 2PG, United Kingdom
Royal Marsden Hospital - Downs Road
London, London, City Of SW7 3RP, United Kingdom
Oxford University Hospitals NHS Trust
Oxford, Oxfordshire OX3 7LE, United Kingdom
University Hospital Birmingham
Birmingham, B15 2TH, United Kingdom

References and documents

Publications

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. PubMed 35226739 ↗

Study documents

Study protocol · May 20, 2022
Statistical analysis plan · Mar 3, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 14, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04074330
Lead sponsor: Takeda
Responsible party: Sponsor
First posted: Aug 30, 2019
Start date: Oct 15, 2019
Primary completion: Apr 26, 2023
Completion: Apr 26, 2023
Results posted: Jun 14, 2024
Last update: Jun 14, 2024

Study contacts

Study Director

study director · Takeda

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in May 2024. You cannot join it, but the record below documents what was studied.

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