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A Study of TAK-981 in People With Advanced Solid Tumors or Cancers in the Immune System

Primary Purpose

Neoplasms, Lymphoma, Hematologic Neoplasms

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TAK-981
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms focused on measuring Drug therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California San Diego Moores Cancer Center
  • Massachusetts General Hospital
  • Barbara Ann Karmanos Cancer Institute
  • HealthPartners Cancer Care Center - Regions Hospital
  • University Hospitals Seidman Cancer Center
  • Fox Chase Cancer Center
  • The University of Texas MD Anderson Cancer Center
  • Froedtert and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1, Dose Escalation Cohort: TAK-981

Phase 2, Cohort A: Nonsquamous NSCLC

Phase 2, Cohort B: Cervical Cancer

Phase 2, Cohort C: MSS-CRC

Phase 2, Cohort D: r/r DLBCL after CAR T-cells therapy

Phase 2, Cohort E: r/r DLBCL without prior cellular therapy

Phase 2, Cohort F: r/r Follicular Lymphoma

Arm Description

TAK-981, intravenously, administered as 60 minute-infusion, once on Days 1, 4, 8, and 11 in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study. If clinical safety, pharmacokinetics, and pharmacodynamics are supportive, the dosing schedule may be modified to evaluate a less intensive administration of TAK-981 on Day 1, or Days 1 and 8, or Day 1, Day 8, and Day 15 in 21-day cycles in participants with advanced or metastatic solid tumors or lymphomas. Dose levels will be escalated based on the Bayesian logistic regression modeling (BLRM). The dose escalation phase will determine the RP2D of TAK-981.

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with nonsquamous non-small cell lung cancer (NSCLC).

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with cervical cancer.

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with microsatellite-stable colorectal cancer (MSS-CRC).

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after prior chimeric antigen receptor (CAR) T-cells therapy.

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory DLBCL that have not received prior cellular therapy.

TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory follicular lymphoma (FL).

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)
Phase 1: Number of Participants Based on Severity of TEAEs
Severity grade will be 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 will be assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.
Phase 1: Number of Participants With Clinically Significant Laboratory Values
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Phase 2: Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors or Lugano classification for lymphoma.

Secondary Outcome Measures

Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981
Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981
Phase 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981
Phase 1, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
Phase 1, Terminal Disposition Phase Half-life (t1/2z) for TAK-981
Phase 1, Total Clearance (CL) After Intravenous Administration for TAK-981
Phase 1, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981
Phase 1: ORR
ORR is defined as percentage of participants who achieve CR and PR through the study (approximately 48 months), as determined by the investigator according to the RECIST V1.1 for participants with solid tumors or Lugano classification for lymphoma.
Phase 1 and Phase 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieve stable disease (SD) or better (determined by the investigator according to RECIST v1.1 criteria for solid tumors or Lugano classification for lymphoma) greater than (>) 6 weeks during the study in the response-evaluable population.
Phase 1 and Phase 2: Duration of Response (DOR)
DOR is the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease for responders (PR or better) and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Phase 1 and Phase 2: Time to Progression (TTP)
TTP is defined as the time from the date of the first dose administration to the date of first documented progressive disease and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Phase 1 and Phase 2: Time to Response (TTR)
TTR is 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 participants with solid tumors or Lugano classification for lymphoma.
Phase 1 and Phase 2: Progression-free Survival (PFS)
PFS is defined as the time from the date of the first dose administration to the date of first documentation of progressive disease or death due to any cause, whichever occurs first and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Phase 1: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Skin/Blood
Phase 2: Number of Participants Reporting one or More TEAEs
Phase 2: Number of Participants Based on Severity of TEAEs
Severity grade will be evaluated as per the NCI CTCAE Version 5.0, except for CRS, which will be assessed by ASTCT consensus grading criteria.
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of the first dose administration to the date of death.

Full Information

First Posted
August 24, 2018
Last Updated
April 12, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT03648372
Brief Title
A Study of TAK-981 in People With Advanced Solid Tumors or Cancers in the Immune System
Official Title
An Open Label, Dose-Escalation, Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics of TAK-981 in Adult Patients With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
April 4, 2024 (Anticipated)
Study Completion Date
October 2, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Lymphoma, Hematologic Neoplasms
Keywords
Drug therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
202 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1, Dose Escalation Cohort: TAK-981
Arm Type
Experimental
Arm Description
TAK-981, intravenously, administered as 60 minute-infusion, once on Days 1, 4, 8, and 11 in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study. If clinical safety, pharmacokinetics, and pharmacodynamics are supportive, the dosing schedule may be modified to evaluate a less intensive administration of TAK-981 on Day 1, or Days 1 and 8, or Day 1, Day 8, and Day 15 in 21-day cycles in participants with advanced or metastatic solid tumors or lymphomas. Dose levels will be escalated based on the Bayesian logistic regression modeling (BLRM). The dose escalation phase will determine the RP2D of TAK-981.
Arm Title
Phase 2, Cohort A: Nonsquamous NSCLC
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with nonsquamous non-small cell lung cancer (NSCLC).
Arm Title
Phase 2, Cohort B: Cervical Cancer
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with cervical cancer.
Arm Title
Phase 2, Cohort C: MSS-CRC
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with microsatellite-stable colorectal cancer (MSS-CRC).
Arm Title
Phase 2, Cohort D: r/r DLBCL after CAR T-cells therapy
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after prior chimeric antigen receptor (CAR) T-cells therapy.
Arm Title
Phase 2, Cohort E: r/r DLBCL without prior cellular therapy
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory DLBCL that have not received prior cellular therapy.
Arm Title
Phase 2, Cohort F: r/r Follicular Lymphoma
Arm Type
Experimental
Arm Description
TAK-981 intravenously administered as 60 minute-infusion in a 21-day treatment cycle for up to approximately 12 months or until discontinuation from the study in participants with relapsed/refractory follicular lymphoma (FL).
Intervention Type
Drug
Intervention Name(s)
TAK-981
Intervention Description
Intravenous infusion.
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)
Time Frame
Up to 48 months
Title
Phase 1: Number of Participants Based on Severity of TEAEs
Description
Severity grade will be 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 will be assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.
Time Frame
Up to 48 months
Title
Phase 1: Number of Participants With Clinically Significant Laboratory Values
Time Frame
Up to 48 months
Title
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame
Up to Cycle 1 (Cycle length is equal to [=] 21 days)
Title
Phase 2: Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors or Lugano classification for lymphoma.
Time Frame
From the first dose until best response is achieved (up to 48 months)
Secondary Outcome Measure Information:
Title
Phase 1, Cmax: Maximum Observed Plasma Concentration for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, Terminal Disposition Phase Half-life (t1/2z) for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, Total Clearance (CL) After Intravenous Administration for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1, Volume of Distribution at Steady State After Intravenous Administration (Vss) for TAK-981
Time Frame
Cycle 1 Day 1: Up to 48 hours post dose; Cycle 1 Day 8: Up to 24 hours post dose (Cycle length =21 days)
Title
Phase 1: ORR
Description
ORR is defined as percentage of participants who achieve CR and PR through the study (approximately 48 months), as determined by the investigator according to the RECIST V1.1 for participants with solid tumors or Lugano classification for lymphoma.
Time Frame
From the first dose until best response is achieved (up to 48 months)
Title
Phase 1 and Phase 2: Disease Control Rate (DCR)
Description
DCR is defined as the percentage of participants who achieve stable disease (SD) or better (determined by the investigator according to RECIST v1.1 criteria for solid tumors or Lugano classification for lymphoma) greater than (>) 6 weeks during the study in the response-evaluable population.
Time Frame
From the first dose until best response is achieved (up to 48 months)
Title
Phase 1 and Phase 2: Duration of Response (DOR)
Description
DOR is the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease for responders (PR or better) and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Time Frame
From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to 48 months)
Title
Phase 1 and Phase 2: Time to Progression (TTP)
Description
TTP is defined as the time from the date of the first dose administration to the date of first documented progressive disease and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Time Frame
From the date of first study drug administration to the date of first documented PD (up to 48 months)
Title
Phase 1 and Phase 2: Time to Response (TTR)
Description
TTR is 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 participants with solid tumors or Lugano classification for lymphoma.
Time Frame
From the date of first study drug administration to the date of first documented PR or better (up to 48 months)
Title
Phase 1 and Phase 2: Progression-free Survival (PFS)
Description
PFS is defined as the time from the date of the first dose administration to the date of first documentation of progressive disease or death due to any cause, whichever occurs first and will be determined by the investigator according to RECIST v1.1 for participants with solid tumors or Lugano classification for lymphoma.
Time Frame
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, through the end of the study (up to 48 months)
Title
Phase 1: Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Skin/Blood
Time Frame
Up to 48 months
Title
Phase 2: Number of Participants Reporting one or More TEAEs
Time Frame
Up to 48 months
Title
Phase 2: Number of Participants Based on Severity of TEAEs
Description
Severity grade will be evaluated as per the NCI CTCAE Version 5.0, except for CRS, which will be assessed by ASTCT consensus grading criteria.
Time Frame
Up to 48 months
Title
Phase 2: Overall Survival (OS)
Description
OS is defined as the time from the date of the first dose administration to the date of death.
Time Frame
From the date of first study drug administration to the date of death (up to 48 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult male or female participants ≥18 years old. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 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. 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). 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. 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. Is willing to provide archival tumor tissue sample, if available. Adequate bone marrow reserve and renal and hepatic function. 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). Consented to undergo serial skin punch biopsies (dose escalation only). Suitable venous access for safe drug administration and the study-required PK and pharmacodynamics sampling. 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.) 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: 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). 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. 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). 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. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse. History of autoimmune disease requiring systemic immunosuppressive therapy. History of immune-related AEs related to treatment with immune checkpoint inhibitors that required treatment discontinuation. History of noninfectious pneumonitis that required steroids or a history of interstitial lung disease. Has evidence of active, noninfectious pneumonitis. Have a significant active infection. Known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency. 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. 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. Participant requires the use of drugs known to prolong QTc interval (during Phase 1 only). History of allogeneic tissue or solid organ transplant. 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
HealthPartners Cancer Care Center - Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
University Hospitals Seidman Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
35226739
Citation
Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.
Results Reference
derived
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b60354db2bf003ab4a092
Description
To obtain more information on the study, click here/on this link

Learn more about this trial

A Study of TAK-981 in People With Advanced Solid Tumors or Cancers in the Immune System

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