Advanced or Metastatic Solid TumorsPhase 1/2NCT04381650
A Study of TAK-981 Given With Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing TAK-981 and Pembrolizumab in people with Advanced or Metastatic Solid Tumors, run by Takeda at 52 sites in 9 countries.
Trial summary
TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors. The study aims are to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- TAK-981 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 52 sitesin 9 countries
- Study dates
- 17 Aug 2020to 29 Oct 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line standard of care treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
- Non-squamous NSCLC for which prior standard first-line treatment containing an anti-programmed cell death protein 1/programmed cell death protein 1 ligand (PD-1/PD-L1) checkpoint inhibitor (CPI) alone or in combination has failed and that has progressed on no more than 1 prior systemic therapy. In Phase 2, participants with nonsquamous NSCLC must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.
- Note: In Phase 1, participants with nonsquamous NSCLC and known driver mutations/genomic aberrations (e.g., 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. In Phase 2, participants with driver mutations are not eligible.
- CPI-naive cervical cancer (squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix) participants for whom prior standard first-line treatment has failed and who have received no more than 1 prior systemic line of therapy for recurrent or Stage IVB cervical cancer. 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 (e.g., weekly cisplatin) is not counted as a systemic chemotherapy regimen.
- CPI-naïve microsatellite stable-colorectal cancer (MSS-CRC) participants for whom prior standard first-line treatment has failed and who have progressed on no more than 3 chemotherapy regimens.
- Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated.
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- Unresectable Stage III or Stage IV cutaneous melanoma that has not received prior therapy in the metastatic setting.
- Note: Participants with acral melanoma are not eligible. Participants who have presented with disease relapse after ≥6 months of the last dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the adjuvant setting are eligible.
- Squamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed. Participant must have not received more than 1 prior systemic therapy and must not have presented with disease progression during the first 6 months of treatment with first-line CPI/anti-PD-(1/L1)-containing therapy.
- Squamous or nonsquamous NSCLC for which prior standard first-line treatment containing an anti-PD-(1/L1) checkpoint inhibitor alone or in combination has failed within 6 months from the initiation of the CPI. Participants must not have received more than 1 prior systemic therapy in the metastatic setting.
- Note: Participants with driver mutations are not eligible.
- Has at least 1 radiologically measurable lesion based on RECIST, Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Has a performance status of 0 or 1 on the Eastern Cooperative Group Oncology (ECOG) Performance Scale.
- Has left ventricular ejection fraction (LVEF) ≥40%; as measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
- Has recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela. Note: Has a neuropathy ≤Grade 2, any grade alopecia, or autoimmune endocrinopathies with stable replacement therapy are permitted.
- Demonstrate adequate organ function as described below:
- Platelet count ≥75.0 × 10^9/L. B. Absolute neutrophil count (ANC) ≥1.0 × 10^9/L. C. Hemoglobin ≥85 g/L (red blood cell [RBC] transfusion allowed ≥14 days before assessment).
- Calculated creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula.
- Aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT) ≤3.0 times the upper limit of normal (ULN), <5.0 times the ULN if liver enzyme elevations are due to liver metastases; bilirubin ≤1.5 times the ULN. Participants with Gilbert's syndrome may have a bilirubin level >1.5 times the ULN, per discussion between the investigator and the medical monitor.
Who cannot join
- History of uncontrolled brain metastasis (evidence of progression by imaging over a period of 4 weeks and/or neurologic symptoms that have not returned to baseline). Participant with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Note: For asymptomatic participants, screening brain imaging is not required.
- 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.
- Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery.
- History of immune-related AEs related to treatment with immune CPIs that required treatment discontinuation.
- Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors.
- Baseline prolongation of the QT interval corrected using Fridericia's formula (QTcF) (e.g., repeated demonstration of QTcF interval >480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes).
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- Has a history of autoimmune disease requiring systemic immunosuppressive therapy with daily doses of prednisone >10 mg/day or equivalent doses, or any other form of immunosuppressive therapy. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency) for endocrinopathies are not considered prohibited forms of systemic treatment of an autoimmune disease.
- Has a history of noninfectious pneumonitis that required steroids or a history of interstitial lung disease.
- Has an evidence of active, non-infectious pneumonitis.
- Has a history of allogeneic tissue or solid organ transplant.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency.
- Has a known hepatitis B virus 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.
- 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, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias >Grade 2, pulmonary embolism or symptomatic cerebrovascular events, or any other serious cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
- Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or has compromised ability to provide written informed consent.
Trial locations and contacts
52 sites in 9 countries.
52 sites in 9 countries
United States18 sites
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
The Center for Cancer and Blood Disorders - PPDS
Bethesda, Maryland, 20817
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
University of Virginia Health System
Charlottesville, Virginia, 22908
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Virginia Cancer Specialists (Fairfax) - USOR
Fairfax, Virginia, 22031
Morristown Medical Center
Morristown, New Jersey, 07960
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Yale Cancer Center
New Haven, Connecticut, 06520
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
University of California Irvine Medical Center
Orange, California, 92868
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15213
Providence Cancer Institute, Franz Clinic
Portland, Oregon, 97213
START South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
HonorHealth
Scottsdale, Arizona, 85258
Stanford Cancer Institute (SCI)
Stanford, California, 94305
Montefiore Einstein Cancer Center - BRANY - PPDS
The Bronx, New York, 10461
Brazil9 sites
Fundacao Pio XII Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-370
Cetus Hospital Dia Oncologia
Belo Horizonte, 30110-140
Instituto de Oncologia Do Parana
Curitiba, Paraná, 80530-010
ONCOSITE Centro de Pesquisa Clinica Em Oncologia
Ijuí, Rio Grande do Sul, 98700-000
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
Porto Alegre, Rio Grande do Sul, 90610-000
INCA Instituto Nacional de Cancer
Rio de Janeiro, 20230-230
Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
Rio de Janeiro, 20941-150
Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto
São José do Rio Preto, São Paulo, 15090-000
Poland7 sites
Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
Bydgoszcz, 85-796
Uniwersyteckie Centrum Kliniczne-Ul. Smoluchowskiego 17
Gdansk, Pomeranian Voivodeship, 80-214
Instytut Medyczny Santa Familia Sp. z o. o.
Lodz, 90-302
Centrum Terapii Wspolczesnej
Lodz, Łódź Voivodeship, 90-242
Specjalistyczna Praktyka Lekarska Slawomir Mandziuk
Lublin, 20-362
Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie
Olsztyn, 10-357
Med-Polonia Sp. z o.o.
Poznan, 60-569
Croatia4 sites
Clinical Hospital Centre Osijek
Osijek, 31000
General Hospital Pula
Pula, 52100
University Hospital Centre Split
Split, 21000
Klinicki bolnicki centar Zagreb
Zagreb, City of Zagreb, 10000
China3 sites
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510060
The First Affiliated Hospital, Zhejiang University School of Medicine - PPDS
Hangzhou, Zhejiang, 310003
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei
Japan3 sites
National Cancer Center Hospital
Chuo-Ku, Tokyo, 104-0045
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Chuo-Ku, Tokyo, 104-0045
National Cancer Center East
Kashiwa-Shi, Chiba, 277-0882
Lithuania3 sites
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Kaunas, Kaunas County, LT-50161
Hospital of Lithuanian University of Health Sciences Kauno klinikos
Kaunas, Kaunas County, LT-50161
National Cancer Institute
Vilnius, Vilnius County, LT-08660
Switzerland3 sites
Universitaetsspital Bern - Inselspital
Bern, 3010
Kantonsspital Muensterlingen
Münsterlingen, Thurgau (de), 8596
Kantonsspital Winterthur
Winterthur, Zurich (de), 8400
Latvia2 sites
Pauls Stradins Clinical University Hospital
Riga, LV-1002
Riga East Clinical University Hospital Latvian Oncology Center
Riga, LV-1079
About this study
Official title: A Phase 1b/2 Study of TAK-981 Plus Pembrolizumab to Evaluate the Safety, Tolerability, and Antitumor Activity of the Combination in Patients With Select Advanced or Metastatic Solid Tumors
TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors.
The study aims are to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab.
Participants will be on this combination treatment for 21-day cycles. They will continue with this treatment for up to 24 months or until participants meet any discontinuation criteria.
Read the detailed description
The drug being tested in this study is called TAK-981. TAK-981 is being tested to treat people who have select advanced or metastatic solid tumors. The study will include a dose escalation phase and a dose expansion phase.
The study will enroll approximately 231 participants, approximately 32 participants in the dose escalation phase 1 and approximately 76 to 199 participants in the 8 cohorts of dose expansion phase 2. Participants will receive escalating doses of TAK-981 and fixed dose of pembrolizumab until recommended phase 2 dose (RP2D) is determined:
- Dose Escalation: TAK-981 + Pembrolizumab (Fixed Dose)
Once Phase 2 doses are identified, participants of select advanced or metastatic solid tumors will receive TAK-981 in below defined cohorts in the expansion phase 2:
- Dose Expansion Phase: Cohort A: Non-squamous Non-small Cell Lung Cancer (NSCLC)
- Dose Expansion Phase: Cohort B: Cervical Cancer
- Dose Expansion Phase: Cohort C: Microsatellite Stable Colorectal Cancer (MSS-CRC)
- Dose Expansion Phase: Cohort D: Cutaneous Melanoma
- Dose Expansion Phase: Cohort E: Squamous NSCLC
- Dose Expansion Phase: Cohort F: Checkpoint Inhibitors (CPI) Refractory Squamous or Nonsquamous NSCLC
This multi-center trial will be conducted worldwide. The overall time to participate in this study is 60 months. Participants will make multiple visits to the clinic, and progression-free survival follow-up for maximum up to 12 months after last dose of study drug.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- TAK-981, Pembrolizumab
- Keywords
- Drug Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-981Drug
TAK-981 IV infusion.
PembrolizumabDrug
Pembrolizumab IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: TAK-981 40 mg + Pembrolizumab | Experimental | Participants received TAK-981 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the recommended Phase 2 dose (RP2D) was determined (for a maximum of 24 months). Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Escalation: TAK-981 60 mg + Pembrolizumab | Experimental | Participants received TAK-981 60 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Escalation: TAK-981 90 mg + Pembrolizumab | Experimental | Participants received TAK-981 90 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Escalation: TAK-981 120 mg + Pembrolizumab | Experimental | Participants received TAK-981 120 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg | Experimental | Participants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg | Experimental | Participants with NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion Phase: Cohort B: Cervical Cancer | Experimental | Participants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion Phase: Cohort C: MSS-CRC | Experimental | Participants with microsatellite stable colorectal cancer (MSS-CRC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion Phase: Cohort D: Cutaneous Melanoma | Experimental | Participants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion Phase: Cohort E: Squamous NSCLC | Experimental | Participants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
| Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC | Experimental | Participants with checkpoint inhibitors (CPI) refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. Receives: Drug: TAK-981; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
Measured: Up to approximately 24 months
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.
Measured: Up to Cycle 1 (each cycle was of 21 days)
Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.
Measured: Up to approximately 24 months
Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Measured: Up to approximately 24 months
Phase 1: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
Measured: Up to approximately 24 months
Phase 1: Number of Participants With Clinically Significant Laboratory Values
Laboratory parameters included clinical chemistry, hematology, and urinalysis. Participants with at least 1 Grade 3 or 4 Lab Abnormalities were reported.
Measured: Up to approximately 24 months
Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1
ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Measured: Up to approximately 25 months
Secondary outcomes (19)
Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
Measured: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phases 1 and 2: Disease Control Rate (DCR)
DCR is defined as the percentage of participants who achieved stable disease (SD) or better (CR + PR + SD determined by the investigator) >6 weeks during the trial in the response-evaluable population.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Durable Response Rate (DRR)
DRR is defined as the rate of objective responses (CR + PR) maintained for at least 6 months initiating at any time within 12 months of commencing therapy.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Duration of Response (DOR)
DOR is defined as a time from the time of first 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.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Progression-free Survival (PFS)
PFS is defined as 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, through the end of the study.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Time to Response (TTR)
TTR is defined as time from the date of the first dose administration to the date of first documented PR or better.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Time to Progression (TTP)
TTP is defined as the from the date of the first dose administration to the date of the first documentation of PD as defined by standard disease criteria.
Measured: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of the first dose administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.
Measured: Up to approximately 25 months
Fold Change From Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes
The level of TAK-981-SUMO adduct formation was evaluated by flow cytometry as the percentage of adduct formed in peripheral blood lymphocytes. Fold change from baseline was calculated as: Post-treatment value / Baseline value. Positive change denotes improvement.
Measured: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
Fold Change From Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes
SUMO pathway inhibition in blood was evaluated by flow cytometry in peripheral blood lymphocytes with an antibody recognizing SUMO 2/3 chains. Fold change from baseline was calculated as: Post-treatment value / Baseline value.
Measured: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to NCI CTCAE, Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.
Measured: Up to approximately 25 months
Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
An AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.
Measured: Up to approximately 25 months
Phase 2: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
Measured: Up to approximately 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2020
- Study start17 Aug 2020
- Primary completion29 Oct 2024
- Study completion29 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This study has 2 Phases. Phase 1 is dose escalation phase with sequential drug assignment. Phase 2 is parallel assignment.
- Masking
- None (open label)
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04381650
- Sponsor's protocol ID
- TAK-981-1502
- Other IDs
- 2020-004325-23, jRCT2031210417
- Status last verified
- Nov 2025
- First submitted
- 6 May 2020
- Last updated
- 10 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Liu H, Seo S, Joung H. TAK-981 enhances antitumor activity in ELT3 uterine leiomyoma cells through the modulation of apoptosis, cell cycle arrest, and autophagy. Biochem Biophys Res Commun. 2025 Jul 12;770:152000. doi: 10.1016/j.bbrc.2025.152000. Epub 2025 May 12.
PubMed 40373381Nakamura A, Grossman S, Song K, Xega K, Zhang Y, Cvet D, Berger A, Shapiro G, Huszar D. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation. Blood. 2022 May 5;139(18):2770-2781. doi: 10.1182/blood.2021014267.
PubMed 35226739
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of TAK-981 Plus Pembrolizumab to Evaluate the Safety, Tolerability, and Antitumor Activity of the Combination in Patients With Select Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04381650
- Acronym / sponsor ID
- TAK-981-1502
- Conditions
- Advanced or Metastatic Solid Tumors
- Keywords
- Drug Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 17 Aug 2020 (actual)
- Primary completion
- 29 Oct 2024 (actual)
- Study completion
- 29 Oct 2024 (actual)
- First posted
- 11 May 2020 (actual)
- Results
- Posted 10 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TAK-981 is being tested in combination with pembrolizumab to treat participants who have select advanced or metastatic solid tumors.
The study aims are to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab.
Participants will be on this combination treatment for 21-day cycles. They will continue with this treatment for up to 24 months or until participants meet any discontinuation criteria.
Detailed description
The drug being tested in this study is called TAK-981. TAK-981 is being tested to treat people who have select advanced or metastatic solid tumors. The study will include a dose escalation phase and a dose expansion phase.
The study will enroll approximately 231 participants, approximately 32 participants in the dose escalation phase 1 and approximately 76 to 199 participants in the 8 cohorts of dose expansion phase 2. Participants will receive escalating doses of TAK-981 and fixed dose of pembrolizumab until recommended phase 2 dose (RP2D) is determined:
- Dose Escalation: TAK-981 + Pembrolizumab (Fixed Dose)
Once Phase 2 doses are identified, participants of select advanced or metastatic solid tumors will receive TAK-981 in below defined cohorts in the expansion phase 2:
- Dose Expansion Phase: Cohort A: Non-squamous Non-small Cell Lung Cancer (NSCLC)
- Dose Expansion Phase: Cohort B: Cervical Cancer
- Dose Expansion Phase: Cohort C: Microsatellite Stable Colorectal Cancer (MSS-CRC)
- Dose Expansion Phase: Cohort D: Cutaneous Melanoma
- Dose Expansion Phase: Cohort E: Squamous NSCLC
- Dose Expansion Phase: Cohort F: Checkpoint Inhibitors (CPI) Refractory Squamous or Nonsquamous NSCLC
This multi-center trial will be conducted worldwide. The overall time to participate in this study is 60 months. Participants will make multiple visits to the clinic, and progression-free survival follow-up for maximum up to 12 months after last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 11
- Model description
- This study has 2 Phases. Phase 1 is dose escalation phase with sequential drug assignment. Phase 2 is parallel assignment.
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: TAK-981 40 mg + Pembrolizumab | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants received TAK-981 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the recommended Phase 2 dose (RP2D) was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 60 mg + Pembrolizumab | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants received TAK-981 60 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 90 mg + Pembrolizumab | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants received TAK-981 90 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Escalation: TAK-981 120 mg + Pembrolizumab | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants received TAK-981 120 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle until the RP2D was determined (for a maximum of 24 months). |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with non-squamous non-small cell lung cancer (NSCLC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort B: Cervical Cancer | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with cervical cancer received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort C: MSS-CRC | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with microsatellite stable colorectal cancer (MSS-CRC) received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort D: Cutaneous Melanoma | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with cutaneous melanoma received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort E: Squamous NSCLC | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
| Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC | Experimental | Drug: TAK-981, Drug: PembrolizumabParticipants with checkpoint inhibitors (CPI) refractory squamous or non-squamous NSCLC received TAK-981 as IV infusion on Days 1, 4, 8 and 11 or Days 1 and 8 in each 21-day Treatment Cycle up to disease progression or 24-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks on Day 1 of 21-day Treatment Cycle for a maximum of 24 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Has a histologically or cytologically documented, advanced (metastatic and/or unresectable) cancer as listed below that is incurable: Note: Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line standard of care treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
- Note: In Phase 1, participants with nonsquamous NSCLC and known driver mutations/genomic aberrations (e.g., 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. In Phase 2, participants with driver mutations are not eligible.
- Note: Participants must have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens if indicated.
- Note: Participants with acral melanoma are not eligible. Participants who have presented with disease relapse after ≥6 months of the last dose of CPI or BRAF-mitogen-activated protein kinase kinase (MEK) inhibitor in the adjuvant setting are eligible.
- Note: Participants with driver mutations are not eligible.
Key exclusion criteria (15 listed)
- History of uncontrolled brain metastasis (evidence of progression by imaging over a period of 4 weeks and/or neurologic symptoms that have not returned to baseline). Participant with treated brain metastases are allowed provided they are radiologically stable, without evidence of progression for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Note: For asymptomatic participants, screening brain imaging is not required.
- 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.
- Major surgery ≤14 days from the first dose of study drug and not recovered fully from any complications from surgery.
- History of immune-related AEs related to treatment with immune CPIs that required treatment discontinuation.
- Receiving or requires the continued use of medications that are known to be strong or moderate inhibitors and inducers of cytochrome P-450 (CYP) 3A4/5 and strong P-glycoprotein (Pgp) inhibitors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-981TAK-981 IV infusion. | Drug | Dose Escalation: TAK-981 120 mg + Pembrolizumab, Dose Escalation: TAK-981 40 mg + Pembrolizumab, Dose Escalation: TAK-981 60 mg + Pembrolizumab, Dose Escalation: TAK-981 90 mg + Pembrolizumab, Dose Expansion Phase: Cohort B: Cervical Cancer, Dose Expansion Phase: Cohort C: MSS-CRC, Dose Expansion Phase: Cohort D: Cutaneous Melanoma, Dose Expansion Phase: Cohort E: Squamous NSCLC, Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC, Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg, Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg |
| PembrolizumabPembrolizumab IV infusion. | Drug | Dose Escalation: TAK-981 120 mg + Pembrolizumab, Dose Escalation: TAK-981 40 mg + Pembrolizumab, Dose Escalation: TAK-981 60 mg + Pembrolizumab, Dose Escalation: TAK-981 90 mg + Pembrolizumab, Dose Expansion Phase: Cohort B: Cervical Cancer, Dose Expansion Phase: Cohort C: MSS-CRC, Dose Expansion Phase: Cohort D: Cutaneous Melanoma, Dose Expansion Phase: Cohort E: Squamous NSCLC, Dose Expansion Phase: Cohort F: CPI Refractory Squamous or Nonsquamous NSCLC, Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 120 mg, Dose Expansion: Cohort A: Non-squamous NSCLC TAK-981 90 mg |
Primary outcome
Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 24 months
An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 except cytokine release syndrome (CRS), which was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Up to Cycle 1 (each cycle was of 21 days)
DLTs were evaluated according to NCI CTCAE Version 5.0 except CRS, which was graded according to ASTCT Consensus Grading for CRS.
Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 24 months
AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the NCI CTCAE Version 5.0, except for CRS, which was assessed by ASTCT Consensus Grading for CRS.
Phase 1: Number of Participants With One or More Serious Adverse Events (SAEs)
Time frame: Up to approximately 24 months
An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Phase 1: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation
Time frame: Up to approximately 24 months
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
Phase 1: Number of Participants With Clinically Significant Laboratory Values
Time frame: Up to approximately 24 months
Laboratory parameters included clinical chemistry, hematology, and urinalysis. Participants with at least 1 Grade 3 or 4 Lab Abnormalities were reported.
Phase 2: Overall Response Rate (ORR) as Assessed by the Investigator According to RECIST, Version 1.1
Time frame: Up to approximately 25 months
ORR is defined as the percentage of participants who achieve Complete Response (CR) and Partial Response (PR) (determined by the investigator) during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
19 secondary outcomes
Phase 1: Cmax: Maximum Observed Plasma Concentration for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: t1/2z: Terminal Disposition Phase Half-life for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: CL: Total Clearance After Intravenous Administration for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phase 1: Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
Time frame: Cycle 1 (each cycle is 21 days) Days 1 and 8 pre-dose and at multiple timepoints (up to 24 hours)
Phases 1 and 2: Disease Control Rate (DCR)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Durable Response Rate (DRR)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Duration of Response (DOR)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Progression-free Survival (PFS)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Time to Response (TTR)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phases 1 and 2: Time to Progression (TTP)
Time frame: Phase 1: Up to approximately 24 months, Phase 2: Up to approximately 25 months
Phase 2: Overall Survival (OS)
Time frame: Up to approximately 25 months
Fold Change From Baseline in TAK-981-/Small Ubiquitin-like Modifier (SUMO) Adduct Formation in Peripheral Blood Lymphocytes
Time frame: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
Fold Change From Baseline in SUMO 2/3 Inhibition in Peripheral Blood Lymphocytes
Time frame: Cycle 1 Day 1 (1 hour, 4 hours, 8 hours) and Day 8 (Pre-dose, 1 hour, 4 hours and 8 hours) (Cycle length = 21 days)
Phase 2: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 25 months
Phase 2: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 25 months
Phase 2: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuation
Time frame: Up to approximately 25 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40373381Liu H, Seo S, Joung H. TAK-981 enhances antitumor activity in ELT3 uterine leiomyoma cells through the modulation of apoptosis, cell cycle arrest, and autophagy. Biochem Biophys Res Commun. 2025 Jul 12;770:152000. doi: 10.1016/j.bbrc.2025.152000. Epub 2025 May 12.
- Derived from this study: PubMed 35226739Nakamura 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.
- To obtain more information about this study, click this link.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
52 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TAK-981 and Pembrolizumab in people with Advanced or Metastatic Solid Tumors, run by Takeda at 52 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in United States, Brazil, Poland, Croatia, China and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) (time frame: Up to approximately 24 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04381650, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.