Neoplasms, Lymphoma, Hematologic Neoplasms
Conditions
Keywords
Drug therapy
Brief summary
This study is in 2 parts. The main aims of the 1st part of the study are to check if people with advanced solid tumors or cancers in the immune system (lymphomas) have side effects from TAK-981, and to check how much TAK-981 they can receive without getting side effects from it. The main aims of the 2nd part of the study are to learn if the condition of people with specific cancers improves after treatment with TAK-981. Another aim is to check for side effects from TAK-981. In the 1st part of the study, participants will receive TAK-981. In the 2nd part of the study, participants with specific tumor types will receive TAK-981 at the recommended phase 2 dose determined during the 1st part of the study. In both parts of the study, participants can receive TAK-981 for up to 1 year or longer if their condition stays improved. Participants will receive TAK-981 through vein.
Detailed description
The drug being tested in this study is called TAK-981. TAK-981 is being tested to evaluate safety, tolerability, preliminary efficacy and PK in participants with advanced or metastatic solid tumors or relapsed/refractory hematologic malignancies. The study will include 2 phases: Phase 1 dose escalation and Phase 2 dose expansion cohorts (cancer treatment expansions). The study will enrol approximately 202 participants, approximately 70 participants in the dose escalation phase, approximately 132 participants in cancer treatment expansion phase. In the dose escalation, dose levels will be escalated based on safety, and available PK and pharmacodynamic data and will also determine the single agent RP2D. Participants in dose expansion phase will be enrolled, once RP2D is determined. There will be 6 cohorts in cancer treatment expansions. * Cohort A: Nonsquamous NSCLC * Cohort B: Cervical cancer * Cohort C: MSS-CRC * Cohort D: Relapsed/refractory DLBCL progressed or relapsed after CAR T-cells therapy * Cohort E: Relapsed/refractory DLBCL that have not received prior cellular therapy * Cohort F: Relapsed/refractory FL This multi-center trial will be conducted in European Union, China and United States. The overall time to participate in this study is approximately 2 years. The overall time to receive treatment in the dose escalation and cancer treatment is approximately 1 year. Based on decision of sponsor, participants with demonstrated clinical benefit can continue treatment beyond 1 year. Participants will make multiple visits to the clinic and will make a final visit 30 days after receiving their last dose of drug or before the start of subsequent anticancer therapy, whichever occurs first for a follow-up assessment.uroped
Interventions
DRUGTAK-981
Intravenous infusion.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult male or female participants ≥18 years old. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 3. Population for Phase 1 dose escalation: * Has histologically or cytologically confirmed advanced (local regionally recurrent not amenable to curative therapy) or metastatic solid tumors who have no standard therapeutic option with a proven clinical benefit, are intolerant, or have refused them. OR * Has relapsed/refractory lymphoma not amenable to therapies with proven clinical benefit or who are intolerant or who refuse them. Participants with low-grade lymphomas such as FL, small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, and marginal zone lymphomas, may not need to exhaust all available therapy. These participants can be enrolled after failure of at least 2 prior systemic therapies, provided that there is not an immediate need for cytoreduction. In these cases, participants who need immediate therapy for tumor bulk are not eligible for this trial. 4. Population for Phase 2 dose expansion cohorts: o Has histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below, that is incurable and for which prior standard first-line treatment has failed: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months before the current tumor recurrence. o Nonsquamous NSCLC that has progressed to 1 prior systemic immune checkpoint inhibitors (CPI)/anti-PD-(1/L1)-containing therapy and no more than 2 lines of therapy. Participants must have not shown evidence of tumor progression during the first 5 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy (cohort A). Note: Participants with known driver mutations/genomic aberrations (example- epidermal growth factor receptor \[EGFR\], B-Raf proto-oncogene mutation V600E \[BRAF V600E\], and ROS proto-oncogene 1 \[ROS1\] sensitizing mutations, neurotrophic receptor tyrosine kinase \[NRTK\] gene fusions, and anaplastic lymphoma kinase \[ALK\] rearrangements) must have also shown progressive disease after treatment with a commercially available targeted therapy. o CPI-naïve cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer (cohort B). Note: The following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric-type adenocarcinoma, clear-cell carcinoma, and mesonephric carcinoma. Histologic confirmation of the original primary tumor is required via pathology report. Note: First-line treatment must have consisted of platinum-containing doublet. Chemotherapy administered concurrently with primary radiation (example- weekly cisplatin) is not counted as a systemic chemotherapy regimen. o CPI-naïve MSS-CRC participants who have progressed on no more than 3 chemotherapy regimens (cohort C). Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated. * Relapsed/refractory DLBCL progressed or relapsed after prior CAR T cell therapy that has received approval by a health authority for the treatment of DLBCL (cohort D). * Relapsed/refractory DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not received prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (cohort E). * Relapsed/refractory 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 F). 5. In Phase 2 only, have at least 1 radiologically measurable lesion based on RECIST v1.1 for participants with solid tumors or Lugano criteria for lymphoma. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Note: In Phase 2 stage 1, have an additional lesion for pretreatment and on-treatment biopsy. 6. In Phase 2 stage 1, willing to consent to mandatory pretreatment and on-treatment tumor biopsy. Note: For fresh tumor biopsies, the lesion must be accessible for a biopsy procedure as assessed by the investigator. 7. Is willing to provide archival tumor tissue sample, if available. 8. Adequate bone marrow reserve and renal and hepatic function. 9. Recovered to Grade 1 or baseline or established as sequelae from all toxic effects of previous therapy (except alopecia, neuropathy, or autoimmune endocrinopathies with stable endocrine replacement therapy, bone marrow parameters \[any of Grade 1 or 2 permitted if directly related to bone marrow involvement). 10. Consented to undergo serial skin punch biopsies (dose escalation only). 11. Suitable venous access for safe drug administration and the study-required PK and pharmacodynamics sampling. 12. Women of childbearing potential participating in this study should avoid becoming pregnant, and male participants should avoid impregnating a female partner. Nonsterilized female participants of reproductive age and male participants should use effective methods of contraception through defined periods during and after study treatment as specified below. Female participants must meet 1 of the following: * Postmenopausal for at least 1 year before the screening visit, or * Surgically sterile, or * If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing of the informed consent form (ICF) through 6 months after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.) 13. Male participants, even if surgically sterilized (that is, status post vasectomy) must agree to 1 of the following: * Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
Exclusion criteria
1. Phase 1 dose escalation and Phase 2 cancer treatment expansion cohorts: o Has received treatment with systemic anticancer treatments or investigational products within 14 days before the first dose of study drug or 5 half-lives, whichever is shorter. Note: Low-dose steroids (oral prednisone or equivalent ≤20 mg per day), hormonal therapy for prostate cancer or breast cancer (as adjuvant treatment), and treatment with bisphosphonates and receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitors are allowed. o Has received extended field radiotherapy ≤4 weeks before the start of treatment (≤2 weeks for limited field radiation for palliation), and who has not recovered to grade 1 or baseline from related side effects of such therapy (except for alopecia). 2. History of any of the following ≤6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, severe noncompensated hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of \>Grade 2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed. 3. Baseline prolongation of the QT interval with Fridericia correction method (QTcF) (example, repeated demonstration of QTcF interval \>480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes). 4. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of adverse events (AEs) or has compromised ability to provide written informed consent. 5. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. 6. History of autoimmune disease requiring systemic immunosuppressive therapy. 7. History of immune-related AEs related to treatment with immune checkpoint inhibitors that required treatment discontinuation. 8. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease. 9. Has evidence of active, noninfectious pneumonitis. 10. Have a significant active infection. 11. Known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency. 12. Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be enrolled but must have an undetectable hepatitis B viral load. 13. Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 3A4/5 (CYP3A4/5) or are strong permeability glycoprotein (P-gp) inhibitors. To participate in this study, participants should discontinue use of such agents for at least 2 weeks (1 week for CYP3A4/5 and P-gp inhibitors) before receiving a dose of TAK-981. 14. Participant requires the use of drugs known to prolong QTc interval (during Phase 1 only). 15. History of allogeneic tissue or solid organ transplant. 16. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy. 17. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants Reporting 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 35.3 months) | TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. Any abnormal laboratory results were considered as TEAEs. |
| 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 35.3 months) | The 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. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was life-threatening consequences; urgent intervention indicated, and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. |
| Phase 1: Duration of TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months) | TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. |
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (Cycle length is equal to [=] 21 days) | DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (\>=) 3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities that were considered by the investigator to be related to study drug and dose-limiting. |
| Phase 2: Overall Response Rate (ORR) | From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 11.2 months) | ORR was defined as percentage of participants who achieved complete response (CR) or partial response (PR) during the study as determined by the investigator according to response assessments based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for solid tumors or Lugano classification for lymphoma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | CL for TAK-981 was reported. |
| Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | Vss for TAK-981 was reported. |
| Phase 1: ORR | From the first dose of study drug until first PD or death, whichever occurred first (up to 34.3 months) | ORR was defined as percentage of participants who achieved CR or PR during the study as determined by the investigator according to response assessments based on RECIST v1.1 for solid tumors or Lugano classification for lymphoma. |
| Phase 1 and 2: Disease Control Rate (DCR) | From first dose of study drug up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | DCR was defined as the percentage of participants who achieved stable disease (SD) (greater than \[\>\] 6 weeks) or better as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. |
| Phase 1 and 2: Duration of Response (DOR) | From first documented confirmed CR or PR until first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | DOR was defined as 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) and determined by the investigator according to RECIST v1.1 with solid tumors or Lugano classification for lymphoma. |
| Phase 1 and 2: Time to Progression (TTP) | From first dose of study drug to the date of the first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | TTP was defined as the time from the date of the first dose administration to the date of first documented PD as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. |
| Phase 1 and 2: Time to Response (TTR) | From first dose of study drug to the date of the first documentation of PR or better, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | TTR was defined as the time from the date of first study drug administration to the date of first documented PR or better by the investigator for responders according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Here, overall number of participants analyzed signifies participants who had CR or PR. |
| Phase 1 and 2: Progression-free Survival (PFS) | From the first dose of study drug to date of PD or death, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | PFS was 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 as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. |
| Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | t1/2z for TAK-981 was reported. |
| Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days) | TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981. |
| Phase 1: Fold Change From Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin | Cycle 1 Day 8 (Cycle length = 21 days) | TAK-981-SUMO adduct formation in skin was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981. |
| Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days) | SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains. |
| Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | Cycle 1 Day 8 (Cycle length = 21 days) | SUMO pathway inhibition in skin was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains. |
| Phase 2: Number of Participants Reporting One or More TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months) | TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. Any abnormal laboratory results were reported as TEAEs. |
| 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 12.2 months) | The severity grade was evaluated as per the CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. |
| Phase 2: Duration of TEAEs | From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months) | TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. |
| Phase 1 and 2: Overall Survival (OS) | From date of first dose of study drug up to death up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2) | OS was defined as the time from the date of the first dose administration to the date of death. |
| Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | Cmax for TAK-981 was reported. |
| Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | Tmax for TAK-981 was reported. |
| Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | AUC0-last for TAK-981 was reported. |
| Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length = 21 days) | AUC0-inf for TAK-981 was reported. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 17 investigative sites in Poland, Belgium, Spain, the United States and China from 01 October 2018 to 14 December 2023.
Pre-assignment details
Participants were enrolled in Phase 1 (Dose Escalation) and in Phase 2 (Dose Expansion) to receive TAK-981 doses.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 3 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 5 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 6 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 3 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 10 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 4 |
| Phase 1, Dose Escalation: TAK-981 15 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 15 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 3 |
| Phase 1, Dose Escalation: TAK-981 25 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 25 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 4 |
| Phase 1, Dose Escalation: TAK-981 40 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 40 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 4 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 7 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 60 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 6 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 6 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 75 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 6 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 8 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 7 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 90 mg, infusion, intravenously, QW on Days 1, 8 and 15 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 7 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 8 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW Participants with relapsed/refractory advanced or metastatic solid tumors or lymphoma received TAK-981 120 mg, infusion, intravenously, QW on Days 1 and 8 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 6 |
| Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 7 |
| Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW Participants with cervical cancer received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 3 |
| Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW Participants with microsatellite-stable colorectal cancer (MSS-CRC) received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 7 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) progressed or relapsed after chimeric antigen receptor (CAR) T-cell therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 4 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW Participants with relapsed/refractory DLBCL that have not received prior cellular therapy received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 3 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW Participants with relapsed/refractory follicular lymphoma received TAK-981 90 mg, infusion, intravenously, BIW on Days 1, 4, 8 and 11 in a 21-day treatment cycle until confirmed disease progression, unacceptable toxicity, or any criterion for withdrawal from the study or discontinuation of study drug occurred. | 1 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 3 | 0 | 5 | 1 | 5 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 2 | 3 | 4 | 3 | 2 | 2 | 3 | 3 | 5 | 5 | 2 | 3 | 3 | 3 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Start of a New Systemic Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Dose Escalation: TAK-981 15 mg BIW | Phase 1, Dose Escalation: TAK-981 25 mg BIW | Phase 1, Dose Escalation: TAK-981 40 mg BIW | Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW | Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW | Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW | Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 9.78 | 61.0 years STANDARD_DEVIATION 14.73 | 52.0 years STANDARD_DEVIATION 11.05 | 66.7 years STANDARD_DEVIATION 10.69 | 59.5 years STANDARD_DEVIATION 5.8 | 65.0 years STANDARD_DEVIATION 4.69 | 59.3 years STANDARD_DEVIATION 10.21 | 62.5 years STANDARD_DEVIATION 9.07 | 60.8 years STANDARD_DEVIATION 10.87 | 62.3 years STANDARD_DEVIATION 10.97 | 60.5 years STANDARD_DEVIATION 9.56 | 62.4 years STANDARD_DEVIATION 14.21 | 64.4 years STANDARD_DEVIATION 7.93 | 59.4 years STANDARD_DEVIATION 11.02 | 57.8 years STANDARD_DEVIATION 8.33 | 64.0 years STANDARD_DEVIATION 6.98 | 53.3 years STANDARD_DEVIATION 2.08 | 51.6 years STANDARD_DEVIATION 13.02 | 56.3 years STANDARD_DEVIATION 18.06 | 71.7 years STANDARD_DEVIATION 5.51 | 53.0 years | 60.3 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 7 Participants | 3 Participants | 7 Participants | 4 Participants | 3 Participants | 1 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 9 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 7 Participants | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 7 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 88 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 5 Participants | 1 Participants | 3 Participants | 3 Participants | 0 Participants | 3 Participants | 1 Participants | 58 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 6 Participants | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 51 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 | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 5 | 0 / 3 | 0 / 4 | 0 / 3 | 1 / 4 | 1 / 4 | 2 / 7 | 1 / 6 | 1 / 6 | 0 / 6 | 2 / 8 | 2 / 7 | 1 / 7 | 1 / 8 | 0 / 6 | 1 / 7 | 1 / 3 | 1 / 7 | 4 / 4 | 2 / 3 | 0 / 1 |
| other Total, other adverse events | 4 / 5 | 3 / 3 | 4 / 4 | 2 / 3 | 4 / 4 | 4 / 4 | 6 / 7 | 6 / 6 | 5 / 6 | 6 / 6 | 7 / 8 | 7 / 7 | 7 / 7 | 8 / 8 | 6 / 6 | 6 / 7 | 3 / 3 | 7 / 7 | 4 / 4 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 3 / 5 | 2 / 3 | 3 / 4 | 1 / 3 | 2 / 4 | 2 / 4 | 3 / 7 | 1 / 6 | 3 / 6 | 1 / 6 | 5 / 8 | 2 / 7 | 2 / 7 | 5 / 8 | 2 / 6 | 2 / 7 | 1 / 3 | 4 / 7 | 2 / 4 | 2 / 3 | 0 / 1 |
Outcome results
Primary
Phase 1: Duration of TEAEs
TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Duration of TEAEs | 3.0 days |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Duration of TEAEs | 4.0 days |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Duration of TEAEs | 1.0 days |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Duration of TEAEs | 3.0 days |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Duration of TEAEs | 4.0 days |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Duration of TEAEs | 9.5 days |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Duration of TEAEs | 4.0 days |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Duration of TEAEs | 3.0 days |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Duration of TEAEs | 8.0 days |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Duration of TEAEs | 2.0 days |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Duration of TEAEs | 4.5 days |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Duration of TEAEs | 5.0 days |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Duration of TEAEs | 2.0 days |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Duration of TEAEs | 3.0 days |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Duration of TEAEs | 4.0 days |
Primary
Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
TEAEs were adverse events (AEs) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. Any abnormal laboratory results were considered as TEAEs.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were evaluated according to NCI CTCAE version 5.0. Grade 5 AE. Hematologic toxicity: Nonfebrile Grade 4 neutropenia/Grade greater than or equal to (\>=) 3 febrile neutropenia; Significant Grade 3 thrombocytopenia; Grade 4 thrombocytopenia. Nonhematologic Grade 3 or higher toxicities; Grade 2 nonhematologic toxicities that were considered by the investigator to be related to study drug and dose-limiting.
Time frame: Cycle 1 (Cycle length is equal to [=] 21 days)
Population: DLT-evaluable analysis set consisted of participants in dose escalation who received all Cycle 1 doses of TAK-981 without experiencing a DLT or who had a DLT during Cycle 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1: Number of Participants With Grade 3 or Higher TEAEs
The 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. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL), Grade 4 was life-threatening consequences; urgent intervention indicated, and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 35.3 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 2 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 0 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 6 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 5 Participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 7 Participants |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
Primary
Phase 2: Overall Response Rate (ORR)
ORR was defined as percentage of participants who achieved complete response (CR) or partial response (PR) during the study as determined by the investigator according to response assessments based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for solid tumors or Lugano classification for lymphoma.
Time frame: From the first dose of study drug until first disease progression (PD) or death, whichever occurred first (up to 11.2 months)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 2: Overall Response Rate (ORR) | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 2: Overall Response Rate (ORR) | 100.0 percentage of participants |
Secondary
Phase 1 and 2: Disease Control Rate (DCR)
DCR was defined as the percentage of participants who achieved stable disease (SD) (greater than \[\>\] 6 weeks) or better as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma.
Time frame: From first dose of study drug up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 25.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 75.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 66.7 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1 and 2: Disease Control Rate (DCR) | 66.7 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 16.7 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1 and 2: Disease Control Rate (DCR) | 66.7 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 42.9 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Disease Control Rate (DCR) | 50.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1 and 2: Disease Control Rate (DCR) | 60.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 42.9 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1 and 2: Disease Control Rate (DCR) | 20.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 71.4 percentage of participants |
| Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 66.7 percentage of participants |
| Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Disease Control Rate (DCR) | 100.0 percentage of participants |
Secondary
Phase 1 and 2: Duration of Response (DOR)
DOR was defined as 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) and determined by the investigator according to RECIST v1.1 with solid tumors or Lugano classification for lymphoma.
Time frame: From first documented confirmed CR or PR until first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened. Here, overall number of participants analyzed signifies participants who had CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Duration of Response (DOR) | 6.93 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Duration of Response (DOR) | 1.41 months |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Duration of Response (DOR) | NA months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Duration of Response (DOR) | 5.55 months |
Secondary
Phase 1 and 2: Overall Survival (OS)
OS was defined as the time from the date of the first dose administration to the date of death.
Time frame: From date of first dose of study drug up to death up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Overall Survival (OS) | 5.49 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | 2.43 months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | 6.14 months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Overall Survival (OS) | NA months |
Secondary
Phase 1 and 2: Progression-free Survival (PFS)
PFS was 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 as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma.
Time frame: From the first dose of study drug to date of PD or death, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 0.95 months |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 0.79 months |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.38 months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.25 months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 2.10 months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 5.49 months |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.18 months |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1 and 2: Progression-free Survival (PFS) | 2.53 months |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.27 months |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1 and 2: Progression-free Survival (PFS) | 2.71 months |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 2.66 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Progression-free Survival (PFS) | 3.94 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1 and 2: Progression-free Survival (PFS) | 2.79 months |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 3.32 months |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1 and 2: Progression-free Survival (PFS) | 1.97 months |
| Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 6.06 months |
| Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 3.78 months |
| Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.18 months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.38 months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 1.09 months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Progression-free Survival (PFS) | 11.17 months |
Secondary
Phase 1 and 2: Time to Progression (TTP)
TTP was defined as the time from the date of the first dose administration to the date of first documented PD as determined by the investigator according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma.
Time frame: From first dose of study drug to the date of the first documentation of PD up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.18 months |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 0.79 months |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.38 months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.25 months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 2.10 months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 5.49 months |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.21 months |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1 and 2: Time to Progression (TTP) | 3.75 months |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.28 months |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1 and 2: Time to Progression (TTP) | 2.71 months |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 6.97 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Time to Progression (TTP) | 3.94 months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1 and 2: Time to Progression (TTP) | 2.79 months |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Time to Progression (TTP) | NA months |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1 and 2: Time to Progression (TTP) | 1.97 months |
| Phase 2, Dose Expansion, Cohort A, NSCLC: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 6.06 months |
| Phase 2, Dose Expansion, Cohort B, Cervical Cancer: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 3.78 months |
| Phase 2, Dose Expansion, Cohort C, MSS-CRC: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.18 months |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.04 months |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 1.09 months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Time to Progression (TTP) | 11.17 months |
Secondary
Phase 1 and 2: Time to Response (TTR)
TTR was defined as the time from the date of first study drug administration to the date of first documented PR or better by the investigator for responders according to RECIST v1.1 for solid tumors or Lugano classification for lymphoma. Here, overall number of participants analyzed signifies participants who had CR or PR.
Time frame: From first dose of study drug to the date of the first documentation of PR or better, whichever occurred first up to 34.3 months (for Phase 1) and up to 11.2 months (for Phase 2)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Time to Response (TTR) | NA months |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1 and 2: Time to Response (TTR) | NA months |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1 and 2: Time to Response (TTR) | NA months |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1 and 2: Time to Response (TTR) | 5.65 months |
Secondary
Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981
AUC0-inf for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 53.5 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 100 h*ng/mL | Geometric Coefficient of Variation 14.7 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 103 h*ng/mL | Geometric Coefficient of Variation 12.8 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 183 h*ng/mL | Geometric Coefficient of Variation 21.9 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 181 h*ng/mL | Geometric Coefficient of Variation 19.5 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 294 h*ng/mL | Geometric Coefficient of Variation 39.2 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 382 h*ng/mL | Geometric Coefficient of Variation 53.5 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 438 h*ng/mL | Geometric Coefficient of Variation 16.2 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 443 h*ng/mL | Geometric Coefficient of Variation 34.7 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1050 h*ng/mL | Geometric Coefficient of Variation 29.9 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 949 h*ng/mL | Geometric Coefficient of Variation 20.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 897 h*ng/mL | Geometric Coefficient of Variation 30.7 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1090 h*ng/mL | Geometric Coefficient of Variation 28 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 967 h*ng/mL | Geometric Coefficient of Variation 20.6 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1040 h*ng/mL | Geometric Coefficient of Variation 26.1 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1330 h*ng/mL | Geometric Coefficient of Variation 17 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1260 h*ng/mL | Geometric Coefficient of Variation 21.9 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1410 h*ng/mL | Geometric Coefficient of Variation 31.4 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1350 h*ng/mL | Geometric Coefficient of Variation 15.5 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1310 h*ng/mL | Geometric Coefficient of Variation 28.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1480 h*ng/mL | Geometric Coefficient of Variation 31.6 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1710 h*ng/mL | Geometric Coefficient of Variation 46.8 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1700 h*ng/mL | Geometric Coefficient of Variation 31.7 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 1360 h*ng/mL | Geometric Coefficient of Variation 32.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1190 h*ng/mL | Geometric Coefficient of Variation 40.8 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 2540 h*ng/mL | Geometric Coefficient of Variation 33.3 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 2590 h*ng/mL | Geometric Coefficient of Variation 60.2 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 8 | 1710 h*ng/mL | Geometric Coefficient of Variation 24.4 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981 | Cycle 1 Day 1 | 2280 h*ng/mL | Geometric Coefficient of Variation 5.6 |
Secondary
Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981
AUC0-last for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 50.1 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 35 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 98.4 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 15.5 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 98.6 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 13.5 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 174 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 178 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.6 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 289 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 40.6 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 364 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 58 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 405 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.3 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 438 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 34.5 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1020 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.1 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 939 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.7 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 906 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30.6 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1070 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 28.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 931 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.5 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1020 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25.8 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1310 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 16.9 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1220 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.1 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1310 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1330 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 15.7 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1230 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.1 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1460 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1650 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.6 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1670 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.9 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1410 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.8 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1300 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 59.2 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 2510 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 30.1 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 3050 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 81.2 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 8 | 1620 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.4 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, AUC0-last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981 | Cycle 1 Day 1 | 1890 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.7 |
Secondary
Phase 1, CL: Total Clearance for TAK-981
CL for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 56.1 liter per hour (L/h) | Geometric Coefficient of Variation 31.1 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 59.8 liter per hour (L/h) | Geometric Coefficient of Variation 14.7 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 58.3 liter per hour (L/h) | Geometric Coefficient of Variation 12.8 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 54.7 liter per hour (L/h) | Geometric Coefficient of Variation 21.9 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 55.3 liter per hour (L/h) | Geometric Coefficient of Variation 19.5 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 51.0 liter per hour (L/h) | Geometric Coefficient of Variation 39.2 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 39.3 liter per hour (L/h) | Geometric Coefficient of Variation 53.5 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 57.1 liter per hour (L/h) | Geometric Coefficient of Variation 16.2 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 56.4 liter per hour (L/h) | Geometric Coefficient of Variation 34.7 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 38.1 liter per hour (L/h) | Geometric Coefficient of Variation 29.9 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 42.2 liter per hour (L/h) | Geometric Coefficient of Variation 20.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 66.9 liter per hour (L/h) | Geometric Coefficient of Variation 30.7 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 55.3 liter per hour (L/h) | Geometric Coefficient of Variation 28 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 62.0 liter per hour (L/h) | Geometric Coefficient of Variation 20.6 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 57.8 liter per hour (L/h) | Geometric Coefficient of Variation 26.1 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 56.3 liter per hour (L/h) | Geometric Coefficient of Variation 17 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 59.4 liter per hour (L/h) | Geometric Coefficient of Variation 21.9 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 53.1 liter per hour (L/h) | Geometric Coefficient of Variation 31.4 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 55.7 liter per hour (L/h) | Geometric Coefficient of Variation 15.5 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 68.8 liter per hour (L/h) | Geometric Coefficient of Variation 28.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 60.7 liter per hour (L/h) | Geometric Coefficient of Variation 31.6 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 52.8 liter per hour (L/h) | Geometric Coefficient of Variation 46.8 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 52.9 liter per hour (L/h) | Geometric Coefficient of Variation 31.7 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 66.0 liter per hour (L/h) | Geometric Coefficient of Variation 32.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 75.6 liter per hour (L/h) | Geometric Coefficient of Variation 40.8 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 47.3 liter per hour (L/h) | Geometric Coefficient of Variation 33.3 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 46.4 liter per hour (L/h) | Geometric Coefficient of Variation 60.2 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 8 | 70.3 liter per hour (L/h) | Geometric Coefficient of Variation 24.4 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, CL: Total Clearance for TAK-981 | Cycle 1 Day 1 | 52.6 liter per hour (L/h) | Geometric Coefficient of Variation 5.6 |
Secondary
Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981
Cmax for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 14.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.6 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 22.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19.7 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 22.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.8 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 33.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.7 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 46.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.3 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 61.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 114 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103.6 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 108 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 39.2 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 124 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 80.9 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 428 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.9 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 314 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37.8 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 343 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26.6 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 417 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.4 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 405 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.6 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 446 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.4 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 738 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37.1 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 846 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.3 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 923 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 685 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30.4 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 654 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.5 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 773 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 852 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.2 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 887 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.5 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 668 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.9 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 653 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 69.6 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 1410 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.8 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 1460 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 65.7 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 8 | 825 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22.3 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981 | Cycle 1 Day 1 | 1100 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36.4 |
Secondary
Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes
TAK-981-SUMO adduct formation in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981.
Time frame: Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days)
Population: Pharmacodynamic analysis set consisted of participants who provided evaluable blood samples (Cycle 1 Day 1 pre-dose sample and at least 1 post-dose sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and here, number analyzed signifies participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.5 fold change | Standard Deviation 0.23 |
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 1.8 fold change | Standard Deviation 0.21 |
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 1.6 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 2.3 fold change | Standard Deviation 0.16 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.9 fold change | Standard Deviation 0.08 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 3.2 fold change | Standard Deviation 0.72 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 2.9 fold change | Standard Deviation 0.62 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.8 fold change | Standard Deviation 0.27 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 2.1 fold change | Standard Deviation 0.04 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 2.9 fold change | Standard Deviation 0.65 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 3.2 fold change | Standard Deviation 1.53 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 2.7 fold change | Standard Deviation 1.36 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.0 fold change | Standard Deviation 0.8 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 3.4 fold change | Standard Deviation 1.55 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 3.8 fold change | Standard Deviation 1.73 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 2.6 fold change | Standard Deviation 1.64 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 2.9 fold change | Standard Deviation 1.38 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 8.0 fold change | Standard Deviation 3.03 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 7.1 fold change | Standard Deviation 2.38 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 5.9 fold change | Standard Deviation 0.83 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.3 fold change | Standard Deviation 0.85 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 3.6 fold change | Standard Deviation 0.92 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 6.7 fold change | Standard Deviation 1.98 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.8 fold change | Standard Deviation 0.7 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 6.0 fold change | Standard Deviation 1.42 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 5.9 fold change | Standard Deviation 1.07 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 7.9 fold change | Standard Deviation 2 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.1 fold change | Standard Deviation 0.74 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.6 fold change | Standard Deviation 0.77 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 7.2 fold change | Standard Deviation 1.84 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 3.3 fold change | Standard Deviation 0.31 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.4 fold change | Standard Deviation 1.25 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 8.4 fold change | Standard Deviation 2.2 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.9 fold change | Standard Deviation 0.87 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 6.3 fold change | Standard Deviation 2.01 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.8 fold change | Standard Deviation 0.44 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 6.1 fold change | Standard Deviation 2.45 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.9 fold change | Standard Deviation 0.1 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 9.6 fold change | Standard Deviation 3.94 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 6.2 fold change | Standard Deviation 2.15 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 6.3 fold change | Standard Deviation 2.63 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.9 fold change | Standard Deviation 1.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.3 fold change | Standard Deviation 2.05 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 7.3 fold change | Standard Deviation 3.17 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 7.5 fold change | Standard Deviation 2.57 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 5.3 fold change | Standard Deviation 0.55 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.1 fold change | Standard Deviation 0.3 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 3.3 fold change | Standard Deviation 1.02 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 6.9 fold change | Standard Deviation 0.89 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 4.3 fold change | Standard Deviation 0.59 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 6.5 fold change | Standard Deviation 2.27 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.7 fold change | Standard Deviation 1.57 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 3.9 fold change | Standard Deviation 0.75 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 7.8 fold change | Standard Deviation 1.59 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.8 fold change | Standard Deviation 0.86 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 5.2 fold change | Standard Deviation 1.49 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 8.7 fold change | Standard Deviation 2.91 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 7.1 fold change | Standard Deviation 1.47 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 6.6 fold change | Standard Deviation 1.68 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 5.9 fold change | Standard Deviation 2.37 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 7.4 fold change | Standard Deviation 2.95 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.2 fold change | Standard Deviation 2.05 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 7.0 fold change | Standard Deviation 2.03 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.1 fold change | Standard Deviation 0.66 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.8 fold change | Standard Deviation 1.1 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.8 fold change | Standard Deviation 1.05 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.5 fold change | Standard Deviation 1.1 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.6 fold change | Standard Deviation 0.92 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 6.9 fold change | Standard Deviation 0.85 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.7 fold change | Standard Deviation 1.02 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 6.0 fold change | Standard Deviation 1.05 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.8 fold change | Standard Deviation 1.19 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 7.5 fold change | Standard Deviation 2.18 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 6.2 fold change | Standard Deviation 1.1 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 9.6 fold change | Standard Deviation 1.74 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 6.9 fold change | Standard Deviation 1.58 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.8 fold change | Standard Deviation 1.46 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.7 fold change | Standard Deviation 1.05 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.4 fold change | Standard Deviation 0.53 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 5.5 fold change | Standard Deviation 1.32 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.4 fold change | Standard Deviation 0.62 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 8.4 fold change | Standard Deviation 2.68 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.9 fold change | Standard Deviation 1.2 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.9 fold change | Standard Deviation 1.42 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 6.2 fold change | Standard Deviation 1.81 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.1 fold change | Standard Deviation 2.12 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.8 fold change | Standard Deviation 2.04 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 6.2 fold change | Standard Deviation 1.32 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.5 fold change | Standard Deviation 2.12 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 3.7 fold change | Standard Deviation 1.06 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 9.2 fold change | Standard Deviation 1.79 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 5.0 fold change | Standard Deviation 0.94 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.9 fold change | Standard Deviation 0.83 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 7.9 fold change | Standard Deviation 1.9 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 5.2 fold change | Standard Deviation 1.06 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 8.1 fold change | Standard Deviation 1.41 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.3 fold change | Standard Deviation 0.38 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.0 fold change | Standard Deviation 1.21 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 5.8 fold change | Standard Deviation 1.22 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 8.2 fold change | Standard Deviation 1.94 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 6.1 fold change | Standard Deviation 1.3 |
Secondary
Phase 1: Fold Change From Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin
TAK-981-SUMO adduct formation in skin was tested by flow cytometry with an antibody recognizing the TAK-981-SUMO adduct formation during the inhibition of the SUMO-activating enzyme by TAK-981.
Time frame: Cycle 1 Day 8 (Cycle length = 21 days)
Population: Pharmacodynamic analysis set consisted of participants who provided evaluable skin biopsies (screening sample and at least 1 on-treatment sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin | 115.57 fold change |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in Levels of TAK-981 SUMO Adduct Formation in Skin | 1343.23 fold change |
Secondary
Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes
SUMO pathway inhibition in peripheral blood lymphocytes was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains.
Time frame: Cycle 1 Day 1: 1, 4 and 8 hours post-dose; Cycle 1 Day 8: Pre-dose, 1, 4 and 8 hours post-dose (Cycle length = 21 days)
Population: Pharmacodynamic analysis set consisted of participants who provided evaluable blood samples (Cycle 1 Day 1 pre-dose sample and at least 1 post-dose sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and here, number analyzed signifies participants evaluable at specified time-points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 1.0 fold change | Standard Deviation 0.04 |
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.2 |
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.9 fold change | Standard Deviation 0.15 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.15 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 1.0 fold change | Standard Deviation 0.16 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 1.0 fold change | Standard Deviation 0.05 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.1 fold change | Standard Deviation 0.1 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.0 fold change | Standard Deviation 0.17 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.07 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.12 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.0 fold change | Standard Deviation 0.15 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.23 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.15 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.9 fold change | Standard Deviation 0.11 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.07 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 1.0 fold change | Standard Deviation 0.14 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.07 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.9 fold change | Standard Deviation 0.11 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.9 fold change | Standard Deviation 0.05 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.1 fold change | Standard Deviation 0.16 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.9 fold change | Standard Deviation 0.1 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.9 fold change | Standard Deviation 0.04 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.08 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.7 fold change | Standard Deviation 0.82 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.9 fold change | Standard Deviation 0.06 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.7 fold change | Standard Deviation 0.65 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.7 fold change | Standard Deviation 0.77 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.09 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 1.6 fold change | Standard Deviation 0.68 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.9 fold change | Standard Deviation 0.18 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 4.1 fold change | Standard Deviation 6.38 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 4.6 fold change | Standard Deviation 7.98 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 4.6 fold change | Standard Deviation 8.2 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 5.5 fold change | Standard Deviation 9.42 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 4.0 fold change | Standard Deviation 6.19 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 4.7 fold change | Standard Deviation 7.88 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 4.6 fold change | Standard Deviation 8.08 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.7 fold change | Standard Deviation 0.3 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.8 fold change | Standard Deviation 0.13 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 2.3 fold change | Standard Deviation 4.03 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.7 fold change | Standard Deviation 0.18 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.1 fold change | Standard Deviation 3.57 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.35 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.7 fold change | Standard Deviation 0.31 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.7 fold change | Standard Deviation 0.25 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.9 fold change | Standard Deviation 0.41 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.7 fold change | Standard Deviation 0.13 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.5 fold change | Standard Deviation 0.66 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.0 fold change | Standard Deviation 0.51 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.9 fold change | Standard Deviation 0.41 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.0 fold change | Standard Deviation 0.76 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.18 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.14 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.5 fold change | Standard Deviation 0.2 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.22 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.0 fold change | Standard Deviation 0.24 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.26 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.24 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 2.5 fold change | Standard Deviation 4.74 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.8 fold change | Standard Deviation 3.05 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.0 fold change | Standard Deviation 0.16 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 2.5 fold change | Standard Deviation 4.49 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.9 fold change | Standard Deviation 3.06 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.22 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.11 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.17 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.11 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.23 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 0.8 fold change | Standard Deviation 0.43 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.13 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.7 fold change | Standard Deviation 0.16 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.8 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.7 fold change | Standard Deviation 0.13 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.1 fold change | Standard Deviation 0.27 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.18 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.7 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.7 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.12 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.7 fold change | Standard Deviation 0.2 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.11 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.14 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.0 fold change | Standard Deviation 0.18 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.09 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.09 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.21 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.11 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.18 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 1.1 fold change | Standard Deviation 0.21 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.5 fold change | Standard Deviation 0.07 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.5 fold change | Standard Deviation 0.14 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 0.7 fold change | Standard Deviation 0.19 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.23 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.17 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 1 hour post-dose | 1.5 fold change | Standard Deviation 2 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 4 hour post-dose | 1.5 fold change | Standard Deviation 1.87 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 4 hour post-dose | 0.6 fold change | Standard Deviation 0.36 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: Pre-dose | 2.8 fold change | Standard Deviation 3.74 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 8 hour post-dose | 0.6 fold change | Standard Deviation 0.35 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 8: 8 hour post-dose | 1.5 fold change | Standard Deviation 2.14 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Blood Lymphocytes | Cycle 1 Day 1: 1 hour post-dose | 0.6 fold change | Standard Deviation 0.22 |
Secondary
Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin
SUMO pathway inhibition in skin was tested by flow cytometry with an antibody recognizing SUMO-2/3 chains.
Time frame: Cycle 1 Day 8 (Cycle length = 21 days)
Population: Pharmacodynamic analysis set consisted of participants who provided evaluable skin biopsies (screening sample and at least 1 on-treatment sample). Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 1.01 fold change | Standard Deviation 0.067 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.71 fold change | Standard Deviation 0.398 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.82 fold change | Standard Deviation 0.088 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.91 fold change | Standard Deviation 0.233 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 1.05 fold change | Standard Deviation 0.122 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.86 fold change | Standard Deviation 0.146 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.72 fold change | Standard Deviation 0.276 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.73 fold change | Standard Deviation 0.298 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.64 fold change | Standard Deviation 0.156 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.71 fold change | Standard Deviation 0.224 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.56 fold change | Standard Deviation 0.136 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.65 fold change | Standard Deviation 0.298 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.78 fold change | Standard Deviation 0.123 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.42 fold change | Standard Deviation 0.376 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: Fold Change From Baseline in SUMO Pathway Inhibition in Skin | 0.44 fold change | Standard Deviation 0.21 |
Secondary
Phase 1: ORR
ORR was defined as percentage of participants who achieved CR or PR during the study as determined by the investigator according to response assessments based on RECIST v1.1 for solid tumors or Lugano classification for lymphoma.
Time frame: From the first dose of study drug until first PD or death, whichever occurred first (up to 34.3 months)
Population: Tumor response-evaluable analysis set consisted of participants who received at least 1 dose of study drug, had sites of measurable disease at baseline, and 1 postbaseline disease assessment, or was discontinued due to symptomatic deterioration or death before a postbaseline evaluation happened.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1: ORR | 33.3 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1: ORR | 16.7 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1: ORR | 14.3 percentage of participants |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1: ORR | 0.0 percentage of participants |
Secondary
Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981
t1/2z for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 5.41 hours |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 7.37 hours |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.74 hours |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.02 hours |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 7.60 hours |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 7.88 hours |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.08 hours |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.38 hours |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 7.87 hours |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.73 hours |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.12 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.47 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 9.18 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.16 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.89 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 9.44 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 4.64 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 2.95 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 9.62 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.45 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.01 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.54 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.32 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.38 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 5.43 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.99 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.20 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 8 | 6.36 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, t1/2z: Terminal Disposition Phase Half-life for TAK-981 | Cycle 1 Day 1 | 8.61 hours |
Secondary
Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981
Tmax for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.17 hours |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.22 hours |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.19 hours |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.03 hours |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.17 hours |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.08 hours |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.03 hours |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.10 hours |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.08 hours |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.18 hours |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.09 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.12 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.09 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.08 hours |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.13 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.05 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.02 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.17 hours |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.05 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.03 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.03 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.12 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.12 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.17 hours |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.15 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.11 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.08 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 8 | 1.13 hours |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981 | Cycle 1 Day 1 | 1.05 hours |
Secondary
Phase 1, Vss: Volume of Distribution at Steady State for TAK-981
Vss for TAK-981 was reported.
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose; Cycle 1 Day 8: pre-dose and at multiple timepoints (up to 24 hours) post-dose (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. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants evaluable at specified time-points. As planned, this outcome measure was analyzed in Phase 1 only.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 332 liters | Geometric Coefficient of Variation 37.9 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 437 liters | Geometric Coefficient of Variation 18.2 |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 385 liters | Geometric Coefficient of Variation 12.9 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 390 liters | Geometric Coefficient of Variation 32 |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 443 liters | Geometric Coefficient of Variation 28.9 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 411 liters | Geometric Coefficient of Variation 72.8 |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 233 liters | Geometric Coefficient of Variation 119.7 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 441 liters | Geometric Coefficient of Variation 41 |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 392 liters | Geometric Coefficient of Variation 39.9 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 173 liters | Geometric Coefficient of Variation 51.7 |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 234 liters | Geometric Coefficient of Variation 36 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 400 liters | Geometric Coefficient of Variation 32.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 359 liters | Geometric Coefficient of Variation 33.5 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 334 liters | Geometric Coefficient of Variation 21.2 |
| Phase 1, Dose Escalation: TAK-981 60 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 367 liters | Geometric Coefficient of Variation 19.2 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 311 liters | Geometric Coefficient of Variation 24 |
| Phase 1, Dose Escalation: TAK-981 75 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 185 liters | Geometric Coefficient of Variation 48.8 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 144 liters | Geometric Coefficient of Variation 84.8 |
| Phase 1, Dose Escalation: TAK-981 75 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 345 liters | Geometric Coefficient of Variation 29.1 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 285 liters | Geometric Coefficient of Variation 39.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 314 liters | Geometric Coefficient of Variation 46.3 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 241 liters | Geometric Coefficient of Variation 76.2 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 290 liters | Geometric Coefficient of Variation 59.4 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 396 liters | Geometric Coefficient of Variation 25.8 |
| Phase 1, Dose Escalation: TAK-981 90 mg QW on Days 1, 8, 15 | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 307 liters | Geometric Coefficient of Variation 60.6 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 271 liters | Geometric Coefficient of Variation 31.3 |
| Phase 1, Dose Escalation: TAK-981 120 mg BIW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 255 liters | Geometric Coefficient of Variation 36.6 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 8 | 322 liters | Geometric Coefficient of Variation 32.7 |
| Phase 1, Dose Escalation: TAK-981 120 mg QW | Phase 1, Vss: Volume of Distribution at Steady State for TAK-981 | Cycle 1 Day 1 | 288 liters | Geometric Coefficient of Variation 27.6 |
Secondary
Phase 2: Duration of TEAEs
TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 2: Duration of TEAEs | 8.5 days |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 2: Duration of TEAEs | 4.0 days |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 2: Duration of TEAEs | 5.0 days |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 2: Duration of TEAEs | 5.0 days |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 2: Duration of TEAEs | 3.0 days |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 2: Duration of TEAEs | 1.0 days |
Secondary
Phase 2: Number of Participants Reporting One or More TEAEs
TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. 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. Any abnormal laboratory results were reported as TEAEs.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 6 Participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 3 Participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 7 Participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 4 Participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 3 Participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 2: Number of Participants Reporting One or More TEAEs | 1 Participants |
Secondary
Phase 2: Number of Participants With Grade 3 or Higher TEAEs
The severity grade was evaluated as per the CTCAE Version 5.0, except for CRS, which was assessed by ASTCT consensus grading. Where Grade 3 was severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4 was 4 Life-threatening consequences; urgent intervention indicated. and Grade 5 was death related to AE. TEAEs were AEs that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug.
Time frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 12.2 months)
Population: Safety analysis set consisted of participants who received at least 1 dose, even if incomplete, of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: TAK-981 3 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 4 Participants |
| Phase 1, Dose Escalation: TAK-981 6 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |
| Phase 1, Dose Escalation: TAK-981 10 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 6 Participants |
| Phase 2, Dose Expansion, Cohort D, DLBCL After CAR T-cells Therapy: TAK-981 90 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 2, Dose Expansion, Cohort E, DLBCL Without Prior Cellular Therapy: TAK-981 90 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 3 Participants |
| Phase 2, Dose Expansion, Cohort F, Follicular Lymphoma: TAK-981 90 mg BIW | Phase 2: Number of Participants With Grade 3 or Higher TEAEs | 1 Participants |