Lymphoma, Non-Hodgkin
Conditions
Keywords
Drug Therapy
Brief 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.
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.
Interventions
DRUGTAK-981
TAK-981 intravenous infusion.
DRUGRituximab
Rituximab intravenous infusion.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each participant must meet all the following inclusion criteria to be enrolled in the study: 1. Participant Population: o. For Phase 1 Dose Escalation: o. aNHL including mantle cell lymphoma and DLBCL histologies such as transformed DLBCL from low-grade lymphoma (follicular or others), DLBCL associated with small-cell infiltration in bone marrow, B-cell lymphoma with intermediate features between DLBCL and Burkitt's lymphoma or with intermediate features between DLBCL and Hodgkin lymphoma, FL grade 3B, and aggressive B-cell lymphoma unclassifiable who must have previously received rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, (Oncovin) and prednisone (R-CHOP) (or equivalent anti-CD20 containing therapy) and 1 additional line of therapy in the r/r setting. o. iNHL (including FL of grades 1-3A and marginal zone lymphoma) refractory to rituximab or to any other anti-CD20 monoclonal antibodies, who have received at least 1 prior systemic therapy for r/r iNHL. o. Rituximab or anti-CD20 refractoriness is defined as failure to respond to, or progression during, any previous rituximab/anti-CD20-containing regimen (monotherapy or combined with chemotherapy), or progression within 6 months of the last rituximab or anti-CD20 dose. Note: The minimum qualifying rituximab/anti-CD20 dose is 1 full cycle (that is, weekly\*4 doses monotherapy or 1 complete dose if combined with chemotherapy). Prior anti-CD20 antibody or cytotoxic drugs may have been administered as single agents or as components of combination therapies. Each repeated course of the same single-agent or combination is considered an independent regimen. o. For Phase 2, the following confirmed CD20+: o. r/r DLBCL progressed or relapsed after a prior CAR T-cells therapy that has received approval by a health authority for the treatment of DLBCL (Cohort A). o. r/r DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not I prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (Cohort B). o. r/r FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least 1 prior line of therapy must have included a CD20-targeted therapy (Cohort C). 2. Must be considered ineligible in the opinion of the investigator, or refused autologous stem-cell transplantation (ASCT). 3. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\<=) 2. 4. Adequate bone marrow function per local laboratory reference range at screening as follows: o Platelet count greater than or equal to (\>=) 75.0\*10\^9/L, Grade 2 thrombocytopenia (platelet count \>=50.0\*10\^9 per liter \[/L\]) is allowed if it is clearly due to marrow involvement with no evidence of myelodysplastic syndrome or hypoplastic bone marrow if found. Absolute neutrophil count (ANC) \>=1.0\*10\^9/L. Hemoglobin \>=85 gram per liter (g/L) (red blood cell \[RBC\] transfusion allowed \>=14 days before assessment). 5. Adequate renal and hepatic function, per local laboratory reference range at screening as follows: * Calculated creatinine clearance \>=30 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula. * Potassium levels \>=lower limit of normal (LLN). For potassium \>upper limit of normal (ULN) discussion with Takeda medical monitor (MM)/designee recommended. * Aspartate aminotransferase and alanine aminotransferase \<=3.0\*the ULN of the institution's normal range; bilirubin \<=1.5\*ULN. Participants with Gilbert's syndrome may have a bilirubin level \>1.5\*ULN, per discussion between the investigator and the medical monitor. 6. Left ventricular ejection fraction (LVEF) \>=40 percent (%); as measured by echocardiogram or multiple gated acquisition (MUGA) scan. 7. Suitable venous access for safe drug administration and the study-required PK and pharmacodynamic sampling. 8. Have at least 1 bidimensionally measurable lesion per Lugano Classification by computed tomography (CT). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 9. Willing to consent to 1 mandatory pretreatment and 1 on-treatment skin biopsy during Phase 1. The skin biopsy entry requirement may be discontinued by the sponsor once there is enough pharmacodynamic evidence of target engagement. 10. For participants enrolled in Phase 2, if available, mandatory submission of archival tumor tissue acquired ≤12 months prior to screening. 11. Recovered to Grade 1, baseline or established as sequela, from all toxic effects of previous therapy (except alopecia, neuropathy, autoimmune endocrinopathies with stable endocrine replacement therapy, neurotoxicity \[Grade 1 or 2 permitted\], or bone marrow parameters \[any of Grade 1, 2, permitted if directly related to bone marrow involvement\]).
Exclusion criteria
Participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 1: Number of Participants With Grade 3 or Higher TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 1: Duration of TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | Up to 42 months | DLTs were evaluated according to NCI CTCAE, Version 5.0. |
| Phase 2: Overall Response Rate (ORR) | Up to 42 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| Phase 1: Overall Response Rate (ORR) | Up to 42 months | 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. |
| Phase 1: Disease Control Rate (DCR) | Up to 42 months | 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. |
| Phase 1: Duration of Response (DOR) | Up to 42 months | 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. |
| Phase 1: Time to Progression (TTP) | Up to 42 months | 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. |
| Phase 1: Progression-Free Survival (PFS) | Up to 42 months | 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. |
| 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 | 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) | The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in blood. Positive change denotes improvement. |
| 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 | Cycle 1 Days 1 and 8 (Cycle length = 21 days) | The level of TAK-981-SUMO adduct formation was evaluated as the percentage of adduct formed in skin. |
| Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Days 1 and 8 (Cycle length = 21 days) | SUMO pathway inhibition in skin was evaluated with skin tissue biopsies by IHC. |
| Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 2: Number of Participants With Grade 3 or Higher TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 2: Duration of TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) | 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. |
| Phase 2: Disease Control Rate (DCR) | Up to 42 months | 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. |
| Phase 2: Duration of Response (DOR) | Up to 42 months | 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. |
| Phase 2: Time to Progression (TTP) | Up to 42 months | 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. |
| Phase 2: Progression-Free Survival (PFS) | Up to 42 months | 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. |
| Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | 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) | SUMO pathway inhibition in blood was evaluated by flow cytometry with an antibody recognizing SUMO2/3 chains. |
| Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
| t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1: Days 1 and 8, pre-infusion and at multiple timepoints (Up to 24 hours) post end of infusion (cycle length=21 days) | 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. |
Countries
Canada, China, France, Germany, Italy, Japan, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
Participants with a diagnosis of Non-Hodgkin Lymphoma were enrolled in this study consisting of Phase 1 (Dose Escalation and Japan-Specific lead-in cohorts), and Phase 2 (Dose Expansion) to receive TAK-981 and/or rituximab.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 4 |
| 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. | 3 |
| 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. | 7 |
| 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. | 8 |
| 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. | 6 |
| 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. | 1 |
| 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. | 3 |
| 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. | 2 |
| 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. | 1 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Escalation (up to 19.36 Months) | Death | 0 | 2 | 0 | 1 | 4 | 1 | 0 | 0 | 0 | 0 |
| Dose Escalation (up to 19.36 Months) | Progressive Disease | 2 | 0 | 0 | 5 | 2 | 2 | 1 | 2 | 0 | 0 |
| Dose Escalation (up to 19.36 Months) | Reason not Specified | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Escalation (up to 19.36 Months) | Site Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Dose Escalation (up to 19.36 Months) | Start of New Systemic Treatment | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Escalation (up to 19.36 Months) | Withdrawal by Subject | 1 | 1 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| Dose Expansion (up to 42 Months) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Dose Expansion (up to 42 Months) | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Japan Lead-in: TAK-981 60mg BIW | 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 | Phase 2 (A): TAK-981 120 mg | Phase 2 (C): TAK-981 120 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.3 years | 64.0 years | 69.3 years | 73.0 years | 57.7 years | 64.8 years | 58.8 years | 61.0 years | 71 years | 55 years | 64.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 7 Participants | 7 Participants | 6 Participants | 1 Participants | 2 Participants | 1 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 7 Participants | 6 Participants | 6 Participants | 0 Participants | 2 Participants | 1 Participants | 31 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 6 Participants | 5 Participants | 0 Participants | 2 Participants | 1 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 4 | 0 / 3 | 1 / 7 | 4 / 8 | 1 / 6 | 0 / 1 | 0 / 3 | 1 / 2 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 | 6 / 7 | 8 / 8 | 6 / 6 | 1 / 1 | 3 / 3 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 2 / 4 | 1 / 3 | 2 / 7 | 5 / 8 | 2 / 6 | 0 / 1 | 0 / 3 | 1 / 2 | 1 / 1 |
Outcome results
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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Duration of TEAEs | 57.0 days |
| Phase 1: TAK-981 40mg QW | Phase 1: Duration of TEAEs | 8.0 days |
| Phase 1: TAK-981 60mg QW | Phase 1: Duration of TEAEs | 13.0 days |
| Phase 1: TAK-981 90mg QW | Phase 1: Duration of TEAEs | 2.0 days |
| Phase 1: TAK-981 90mg BIW | Phase 1: Duration of TEAEs | 11.0 days |
| Phase 1: TAK-981 120mg QW | Phase 1: Duration of TEAEs | 10.0 days |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Duration of TEAEs | 2.0 days |
Primary
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
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Phase 1: TAK-981 40mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Phase 1: TAK-981 60mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Phase 1: TAK-981 90mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Phase 1: TAK-981 90mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Phase 1: TAK-981 120mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) Per Dose Level | 0 Participants |
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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
| Phase 1: TAK-981 40mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 4 Participants |
| Phase 1: TAK-981 60mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
| Phase 1: TAK-981 90mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 1: TAK-981 90mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 7 Participants |
| Phase 1: TAK-981 120mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1: TAK-981 40mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1: TAK-981 60mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1: TAK-981 90mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1: TAK-981 90mg BIW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 8 Participants |
| Phase 1: TAK-981 120mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
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.
Time frame: Up to 42 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Overall Response Rate (ORR) | 50 percentage of participants |
| Phase 1: TAK-981 40mg QW | Phase 2: Overall Response Rate (ORR) | 100 percentage of participants |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 151 h.ng/ml | Standard Deviation 15.1 |
| Phase 1: TAK-981 10mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 150 h.ng/ml | Standard Deviation 19.2 |
| Phase 1: TAK-981 40mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 498 h.ng/ml | Standard Deviation 128 |
| Phase 1: TAK-981 40mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 538 h.ng/ml | Standard Deviation 242 |
| Phase 1: TAK-981 60mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1110 h.ng/ml | Standard Deviation 465 |
| Phase 1: TAK-981 60mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1210 h.ng/ml | Standard Deviation 514 |
| Phase 1: TAK-981 90mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1360 h.ng/ml | Standard Deviation 398 |
| Phase 1: TAK-981 90mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1330 h.ng/ml | Standard Deviation 359 |
| Phase 1: TAK-981 90mg BIW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1640 h.ng/ml | Standard Deviation 445 |
| Phase 1: TAK-981 90mg BIW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1780 h.ng/ml | Standard Deviation 490 |
| Phase 1: TAK-981 120mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1600 h.ng/ml | Standard Deviation 550 |
| Phase 1: TAK-981 120mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1830 h.ng/ml | Standard Deviation 344 |
| Japan Lead-in: TAK-981 60mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1560 h.ng/ml | Standard Deviation 114 |
| Japan Lead-in: TAK-981 60mg QW | AUC0-∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1460 h.ng/ml | Standard Deviation 382 |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 146 hours*ng/mL | Standard Deviation 15 |
| Phase 1: TAK-981 10mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 140 hours*ng/mL | Standard Deviation 25.6 |
| Phase 1: TAK-981 40mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 477 hours*ng/mL | Standard Deviation 130 |
| Phase 1: TAK-981 40mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 517 hours*ng/mL | Standard Deviation 236 |
| Phase 1: TAK-981 60mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 1070 hours*ng/mL | Standard Deviation 456 |
| Phase 1: TAK-981 60mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 1160 hours*ng/mL | Standard Deviation 510 |
| Phase 1: TAK-981 90mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 1310 hours*ng/mL | Standard Deviation 380 |
| Phase 1: TAK-981 90mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 1290 hours*ng/mL | Standard Deviation 351 |
| Phase 1: TAK-981 90mg BIW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 1490 hours*ng/mL | Standard Deviation 475 |
| Phase 1: TAK-981 90mg BIW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 1640 hours*ng/mL | Standard Deviation 483 |
| Phase 1: TAK-981 120mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 1640 hours*ng/mL | Standard Deviation 484 |
| Phase 1: TAK-981 120mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 1780 hours*ng/mL | Standard Deviation 333 |
| Japan Lead-in: TAK-981 60mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 1 | 1520 hours*ng/mL | Standard Deviation 103 |
| Japan Lead-in: TAK-981 60mg QW | AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981 | Cycle 1 Day 8 | 1420 hours*ng/mL | Standard Deviation 356 |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 66.8 litres per hour (L/h) | Standard Deviation 6.37 |
| Phase 1: TAK-981 10mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 67.4 litres per hour (L/h) | Standard Deviation 8.23 |
| Phase 1: TAK-981 40mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 83.8 litres per hour (L/h) | Standard Deviation 17.8 |
| Phase 1: TAK-981 40mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 75.2 litres per hour (L/h) | Standard Deviation 43.8 |
| Phase 1: TAK-981 60mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 65.2 litres per hour (L/h) | Standard Deviation 37 |
| Phase 1: TAK-981 60mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 57.8 litres per hour (L/h) | Standard Deviation 26.2 |
| Phase 1: TAK-981 90mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 72.7 litres per hour (L/h) | Standard Deviation 27.2 |
| Phase 1: TAK-981 90mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 73.3 litres per hour (L/h) | Standard Deviation 25.9 |
| Phase 1: TAK-981 90mg BIW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 58.2 litres per hour (L/h) | Standard Deviation 15.5 |
| Phase 1: TAK-981 90mg BIW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 53.9 litres per hour (L/h) | Standard Deviation 14.6 |
| Phase 1: TAK-981 120mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 81.8 litres per hour (L/h) | Standard Deviation 24.7 |
| Phase 1: TAK-981 120mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 68.0 litres per hour (L/h) | Standard Deviation 16.1 |
| Japan Lead-in: TAK-981 60mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 38.6 litres per hour (L/h) | Standard Deviation 2.78 |
| Japan Lead-in: TAK-981 60mg QW | CL: Total Clearance After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 43.2 litres per hour (L/h) | Standard Deviation 13.1 |
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 39.8 nanograms per millilitre (ng/ml) | Standard Deviation 19.1 |
| Phase 1: TAK-981 10mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 51.4 nanograms per millilitre (ng/ml) | Standard Deviation 13.9 |
| Phase 1: TAK-981 40mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 184 nanograms per millilitre (ng/ml) | Standard Deviation 139 |
| Phase 1: TAK-981 40mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 200 nanograms per millilitre (ng/ml) | Standard Deviation 152 |
| Phase 1: TAK-981 60mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 444 nanograms per millilitre (ng/ml) | Standard Deviation 323 |
| Phase 1: TAK-981 60mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 595 nanograms per millilitre (ng/ml) | Standard Deviation 410 |
| Phase 1: TAK-981 90mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 648 nanograms per millilitre (ng/ml) | Standard Deviation 214 |
| Phase 1: TAK-981 90mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 600 nanograms per millilitre (ng/ml) | Standard Deviation 146 |
| Phase 1: TAK-981 90mg BIW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 810 nanograms per millilitre (ng/ml) | Standard Deviation 305 |
| Phase 1: TAK-981 90mg BIW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 967 nanograms per millilitre (ng/ml) | Standard Deviation 299 |
| Phase 1: TAK-981 120mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 740 nanograms per millilitre (ng/ml) | Standard Deviation 491 |
| Phase 1: TAK-981 120mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 981 nanograms per millilitre (ng/ml) | Standard Deviation 272 |
| Japan Lead-in: TAK-981 60mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 833 nanograms per millilitre (ng/ml) | Standard Deviation 73.3 |
| Japan Lead-in: TAK-981 60mg QW | Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 731 nanograms per millilitre (ng/ml) | Standard Deviation 346 |
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.
Time frame: Up to 42 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Disease Control Rate (DCR) | 100 percenage of participants |
| Phase 1: TAK-981 40mg QW | Phase 1: Disease Control Rate (DCR) | 50.0 percenage of participants |
| Phase 1: TAK-981 60mg QW | Phase 1: Disease Control Rate (DCR) | 100 percenage of participants |
| Phase 1: TAK-981 90mg QW | Phase 1: Disease Control Rate (DCR) | 28.6 percenage of participants |
| Phase 1: TAK-981 90mg BIW | Phase 1: Disease Control Rate (DCR) | 16.7 percenage of participants |
| Phase 1: TAK-981 120mg QW | Phase 1: Disease Control Rate (DCR) | 50.0 percenage of participants |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Disease Control Rate (DCR) | 0 percenage of participants |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Disease Control Rate (DCR) | 33.3 percenage of participants |
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.
Time frame: Up to 42 months
Population: 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. Overall number of participants analyzed is the number of participants with events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Duration of Response (DOR) | 8.31 months |
| Phase 1: TAK-981 90mg QW | Phase 1: Duration of Response (DOR) | 2.73 months |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Duration of Response (DOR) | 8.94 months |
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 4.6 ratio | Standard Deviation 0.19 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 3.7 ratio | Standard Deviation 0.27 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 8 /Predose | 1.8 ratio | Standard Deviation 0.13 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 4.1 ratio | Standard Deviation 0.54 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 3.6 ratio | Standard Deviation 0.66 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 3.9 ratio | Standard Deviation 0.19 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 3.2 ratio | Standard Deviation 0.55 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 4.2 ratio | Standard Deviation 1.34 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 6.6 ratio | Standard Deviation 0.96 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 4.5 ratio | Standard Deviation 1.22 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 4.7 ratio | Standard Deviation 1.18 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 5.7 ratio | Standard Deviation 1.47 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 8 /Predose | 1.9 ratio | Standard Deviation 0.68 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 6.2 ratio | Standard Deviation 1.87 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 5.1 ratio | Standard Deviation 0.7 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /Predose | 1.9 ratio | Standard Deviation 0.27 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 4.0 ratio | Standard Deviation 0.49 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 4.7 ratio | Standard Deviation 1.28 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 6.3 ratio | Standard Deviation 1.02 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 4.1 ratio | Standard Deviation 1.24 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 8.0 ratio | Standard Deviation 0.87 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 6.1 ratio | Standard Deviation 2.16 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 5.3 ratio | Standard Deviation 1.97 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 6.7 ratio | Standard Deviation 1.07 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 9.1 ratio | Standard Deviation 3.21 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 5.6 ratio | Standard Deviation 1.05 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 9.5 ratio | Standard Deviation 1.04 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 8 /Predose | 2.5 ratio | Standard Deviation 0.88 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 8 /Predose | 2.8 ratio | Standard Deviation 0.51 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 7.6 ratio | Standard Deviation 0.73 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 4.9 ratio | Standard Deviation 1.69 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 4.6 ratio | Standard Deviation 0.72 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 7.8 ratio | Standard Deviation 0.61 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 5.8 ratio | Standard Deviation 0.65 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 4.0 ratio | Standard Deviation 1.43 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 8 /Predose | 2.8 ratio | Standard Deviation 1.5 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 11.6 ratio | Standard Deviation 6.34 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 5.2 ratio | Standard Deviation 0.64 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 5.6 ratio | Standard Deviation 1.73 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 6.5 ratio | Standard Deviation 0.56 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 9.9 ratio | Standard Deviation 2.84 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 7.1 ratio | Standard Deviation 2.83 |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /Predose | 1.1 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 2.9 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 4.9 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 5.0 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 3.0 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 1 /1 Hour Postdose | 6.7 ratio | Standard Deviation 1.42 |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 1 /8 Hours Postdose | 3.3 ratio | Standard Deviation 0.32 |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 1 /4 Hours Postdose | 4.1 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 8 /1 Hour Postdose | 5.4 ratio | Standard Deviation 0.69 |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 8 /8 Hours Postdose | 3.3 ratio | Standard Deviation 0.38 |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 8 /4 Hours Postdose | 4.3 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 8 /Predose | 1.6 ratio | Standard Deviation 0.17 |
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.
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.9 ratio | Standard Deviation 0.1 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 1.0 ratio | Standard Deviation 0.05 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 0.9 ratio | Standard Deviation 0.09 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.9 ratio | Standard Deviation 0.05 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.9 ratio | Standard Deviation 0.07 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.9 ratio | Standard Deviation 0.09 |
| Phase 1: TAK-981 10mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.9 ratio | Standard Deviation 0.09 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.7 ratio | Standard Deviation 0.37 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.8 ratio | Standard Deviation 0.34 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.8 ratio | Standard Deviation 0.17 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.8 ratio | Standard Deviation 0.15 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.8 ratio | Standard Deviation 0.15 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 1.1 ratio | Standard Deviation 0.37 |
| Phase 1: TAK-981 40mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.7 ratio | Standard Deviation 0.31 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.5 ratio | Standard Deviation 0.23 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 0.8 ratio | Standard Deviation 0.12 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.04 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.5 ratio | Standard Deviation 0.34 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.36 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.33 |
| Phase 1: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.19 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.6 ratio | Standard Deviation 0.2 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.13 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.5 ratio | Standard Deviation 0.15 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.05 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.15 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.6 ratio | Standard Deviation 0.11 |
| Phase 1: TAK-981 90mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 1.1 ratio | Standard Deviation 0.46 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 0.9 ratio | Standard Deviation 0.07 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.26 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.4 ratio | Standard Deviation 0.3 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.22 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.14 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.7 ratio | Standard Deviation 0.05 |
| Phase 1: TAK-981 90mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.5 ratio | Standard Deviation 0.35 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 1.1 ratio | Standard Deviation 0.25 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.6 ratio | Standard Deviation 0.1 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.7 ratio | Standard Deviation 0.28 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 0.7 ratio | Standard Deviation 0.1 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 0.9 ratio | Standard Deviation 0.14 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.6 ratio | Standard Deviation 0.22 |
| Phase 1: TAK-981 120mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.7 ratio | Standard Deviation 0.17 |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 0.2 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.2 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.1 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.1 ratio | — |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.2 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /1 Hour Postdose | 0.8 ratio | Standard Deviation 0.33 |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /8 Hours Postdose | 0.8 ratio | Standard Deviation 0.24 |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 1 /4 Hours Postdose | 1.0 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /1 Hour Postdose | 0.5 ratio | Standard Deviation 0.25 |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /8 Hours Postdose | 0.7 ratio | Standard Deviation 0.31 |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /4 Hours Postdose | 1.2 ratio | — |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood as Assessed by Flow Cytometry During Phase 1 | Cycle 1 Day 8 /Predose | 0.7 ratio | Standard Deviation 0.33 |
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.
Time frame: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0.03 |
| Phase 1: TAK-981 10mg QW | 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 | Cycle 1 Day 8 | 1.2 % adduct positive | Standard Deviation 1.15 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0 |
| Phase 1: TAK-981 40mg QW | 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 | Cycle 1 Day 8 | 15.8 % adduct positive | Standard Deviation 12.7 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0 |
| Phase 1: TAK-981 60mg QW | 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 | Cycle 1 Day 8 | 27.0 % adduct positive | Standard Deviation 12.29 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0 |
| Phase 1: TAK-981 90mg QW | 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 | Cycle 1 Day 8 | 22.6 % adduct positive | Standard Deviation 9.47 |
| Phase 1: TAK-981 90mg BIW | 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 | Cycle 1 Day 8 | 59.7 % adduct positive | — |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0 |
| Phase 1: TAK-981 120mg QW | 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 | Cycle 1 Day 8 | 11.2 % adduct positive | Standard Deviation 11.35 |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | — |
| Japan Lead-in: TAK-981 60mg QW | 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 | Cycle 1 Day 8 | 1.4 % adduct positive | — |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 1 /Predose | 0.0 % adduct positive | Standard Deviation 0 |
| Japan Lead-in: TAK-981 60mg BIW | 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 | Cycle 1 Day 8 | 29.5 % adduct positive | Standard Deviation 19.88 |
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.
Time frame: Up to 42 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Overall Response Rate (ORR) | 33.3 percentage of participants |
| Phase 1: TAK-981 40mg QW | Phase 1: Overall Response Rate (ORR) | 50.0 percentage of participants |
| Phase 1: TAK-981 60mg QW | Phase 1: Overall Response Rate (ORR) | 66.7 percentage of participants |
| Phase 1: TAK-981 90mg QW | Phase 1: Overall Response Rate (ORR) | 14.3 percentage of participants |
| Phase 1: TAK-981 90mg BIW | Phase 1: Overall Response Rate (ORR) | 0 percentage of participants |
| Phase 1: TAK-981 120mg QW | Phase 1: Overall Response Rate (ORR) | 33.3 percentage of participants |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: Overall Response Rate (ORR) | 0 percentage of participants |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Overall Response Rate (ORR) | 33.3 percentage of participants |
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.
Time frame: Up to 42 months
Population: 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. Overall number of participants analyzed are the number of participants with events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Progression-Free Survival (PFS) | 12.42 months |
| Phase 1: TAK-981 90mg QW | Phase 1: Progression-Free Survival (PFS) | 1.58 months |
| Phase 1: TAK-981 90mg BIW | Phase 1: Progression-Free Survival (PFS) | 2.33 months |
| Phase 1: TAK-981 120mg QW | Phase 1: Progression-Free Survival (PFS) | NA months |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Progression-Free Survival (PFS) | 13.18 months |
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.
Time frame: Cycle 1 Days 1 and 8 (Cycle length = 21 days)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 83.40383 % Sumo 2/3 positive | Standard Deviation 2.692876 |
| Phase 1: TAK-981 10mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 82.26130 % Sumo 2/3 positive | Standard Deviation 2.017705 |
| Phase 1: TAK-981 40mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 87.74383 % Sumo 2/3 positive | Standard Deviation 5.142812 |
| Phase 1: TAK-981 40mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 79.34405 % Sumo 2/3 positive | Standard Deviation 10.262143 |
| Phase 1: TAK-981 60mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 89.60727 % Sumo 2/3 positive | Standard Deviation 5.52853 |
| Phase 1: TAK-981 60mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 55.69903 % Sumo 2/3 positive | Standard Deviation 19.325964 |
| Phase 1: TAK-981 90mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 89.63755 % Sumo 2/3 positive | Standard Deviation 4.044536 |
| Phase 1: TAK-981 90mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 52.54200 % Sumo 2/3 positive | Standard Deviation 15.606775 |
| Phase 1: TAK-981 90mg BIW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 51.84200 % Sumo 2/3 positive | — |
| Phase 1: TAK-981 120mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 75.79235 % Sumo 2/3 positive | Standard Deviation 2.586486 |
| Phase 1: TAK-981 120mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 63.14625 % Sumo 2/3 positive | Standard Deviation 15.415286 |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 86.85370 % Sumo 2/3 positive | — |
| Japan Lead-in: TAK-981 60mg QW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 69.68880 % Sumo 2/3 positive | — |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 1 /Predose | 69.65077 % Sumo 2/3 positive | Standard Deviation 19.035919 |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: SUMO Pathway Inhibition in Skin as Assessed by Immunohistochemistry (IHC) During Phase 1 | Cycle 1 Day 8 | 41.79763 % Sumo 2/3 positive | Standard Deviation 21.796849 |
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.
Time frame: Up to 42 months
Population: 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. Overall number of participants analyzed is the number of participants with events.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 1: Time to Progression (TTP) | 12.42 months |
| Phase 1: TAK-981 90mg QW | Phase 1: Time to Progression (TTP) | 1.58 months |
| Phase 1: TAK-981 90mg BIW | Phase 1: Time to Progression (TTP) | 1.48 months |
| Phase 1: TAK-981 120mg QW | Phase 1: Time to Progression (TTP) | NA months |
| Japan Lead-in: TAK-981 60mg BIW | Phase 1: Time to Progression (TTP) | 13.18 months |
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.
Time frame: Up to 42 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Disease Control Rate (DCR) | 1 percentage of participants |
| Phase 1: TAK-981 40mg QW | Phase 2: Disease Control Rate (DCR) | 1 percentage of participants |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Duration of Response (DOR) | 3.32 months |
| Phase 1: TAK-981 40mg QW | Phase 2: Duration of Response (DOR) | 0.03 months |
Secondary
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)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Duration of TEAEs | 8.0 days |
| Phase 1: TAK-981 40mg QW | Phase 2: Duration of TEAEs | 2.0 days |
Secondary
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)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 1: TAK-981 40mg QW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
Secondary
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)
Population: Safety Analysis Set consisted of participants who have received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
| Phase 1: TAK-981 40mg QW | Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Progression-Free Survival (PFS) | 3.15 months |
| Phase 1: TAK-981 40mg QW | Phase 2: Progression-Free Survival (PFS) | 1.48 months |
Secondary
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: TAK-981 10mg QW | Phase 2: Time to Progression (TTP) | 5.32 months |
| Phase 1: TAK-981 40mg QW | Phase 2: Time to Progression (TTP) | 1.48 months |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: TAK-981 10mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.03 hours |
| Phase 1: TAK-981 10mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.06 hours |
| Phase 1: TAK-981 40mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.88 hours |
| Phase 1: TAK-981 40mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.92 hours |
| Phase 1: TAK-981 60mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 6.02 hours |
| Phase 1: TAK-981 60mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.77 hours |
| Phase 1: TAK-981 90mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.78 hours |
| Phase 1: TAK-981 90mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.75 hours |
| Phase 1: TAK-981 90mg BIW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 4.88 hours |
| Phase 1: TAK-981 90mg BIW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.59 hours |
| Phase 1: TAK-981 120mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.78 hours |
| Phase 1: TAK-981 120mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.73 hours |
| Japan Lead-in: TAK-981 60mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.45 hours |
| Japan Lead-in: TAK-981 60mg QW | t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.91 hours |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1: TAK-981 10mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.17 hours |
| Phase 1: TAK-981 10mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.15 hours |
| Phase 1: TAK-981 40mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.08 hours |
| Phase 1: TAK-981 40mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.15 hours |
| Phase 1: TAK-981 60mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 0.95 hours |
| Phase 1: TAK-981 60mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.14 hours |
| Phase 1: TAK-981 90mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.14 hours |
| Phase 1: TAK-981 90mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.08 hours |
| Phase 1: TAK-981 90mg BIW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.17 hours |
| Phase 1: TAK-981 90mg BIW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.05 hours |
| Phase 1: TAK-981 120mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.28 hours |
| Phase 1: TAK-981 120mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.11 hours |
| Japan Lead-in: TAK-981 60mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.12 hours |
| Japan Lead-in: TAK-981 60mg QW | Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.12 hours |
Secondary
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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: TAK-981 10mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 396 litres (L) | Standard Deviation 72.8 |
| Phase 1: TAK-981 10mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 352 litres (L) | Standard Deviation 79.9 |
| Phase 1: TAK-981 40mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 517 litres (L) | Standard Deviation 202 |
| Phase 1: TAK-981 40mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 456 litres (L) | Standard Deviation 278 |
| Phase 1: TAK-981 60mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 406 litres (L) | Standard Deviation 277 |
| Phase 1: TAK-981 60mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 332 litres (L) | Standard Deviation 211 |
| Phase 1: TAK-981 90mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 352 litres (L) | Standard Deviation 136 |
| Phase 1: TAK-981 90mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 347 litres (L) | Standard Deviation 110 |
| Phase 1: TAK-981 90mg BIW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 255 litres (L) | Standard Deviation 75.5 |
| Phase 1: TAK-981 90mg BIW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 273 litres (L) | Standard Deviation 201 |
| Phase 1: TAK-981 120mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 410 litres (L) | Standard Deviation 156 |
| Phase 1: TAK-981 120mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 307 litres (L) | Standard Deviation 95 |
| Japan Lead-in: TAK-981 60mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 1 | 154 litres (L) | Standard Deviation 1.72 |
| Japan Lead-in: TAK-981 60mg QW | Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 | Cycle 1 Day 8 | 189 litres (L) | Standard Deviation 68 |