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Advanced LymphomaPhase 1NCT06223542

Studying TAK-243 in Patients With Advanced Cancer

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
1 siteUnited States
Study dates
24 Mar 2025to 15 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Patients with histologically documented advanced or metastatic solid tumors with relapsed or refractory disease who have received standard-of-care or approved therapies known to confer clinical benefit, or patients with aggressive lymphomas who have received ≥ 2 prior lines of lymphoma-directed therapy and who do not have remaining effective treatment options (including transplant). Additionally, patients with indolent lymphomas must meet criteria for treatment.
  • Patients must have measurable or evaluable disease
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin >= 9 g/dL (patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed)
  • Absolute neutrophil count >= 1,000/mcL
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  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN OR =< 5 x institutional upper limit of normal for patients with liver metastases at baseline
  • Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 by Cockcroft-Gault
  • Any prior therapy must have been completed >= 4 weeks, or >= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed >= 4 weeks prior to enrollment; prior palliative radiation should have been completed >= 2 weeks prior to enrollment. Patients must be >= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities
  • Female patients who:
  • Are postmenopausal (age-related amenorrhea >= 12 consecutive months or follicle-stimulating hormone > 40 mIU/mL), for at least 1 year before the screening visit, OR
  • Are surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), 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 the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
  • The effects of TAK-243 on the developing human fetus are unknown. For this reason and because ubiquitin-activating enzyme inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of TAK-243 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to provide blood for research purposes
  • For expansion phase patients, willingness to undergo 2 core needle biopsy procedures for research purposes if there is a lesion or lesions amenable to repeat biopsy
  • Patients on anticoagulation therapy are eligible for this study in the absence of anticipated drug-drug interactions (DDI) between the anticoagulation agent and TAK-243. If DDI are anticipated and another anticoagulation agent that is compatible with TAK-243 exists, the patient will be transitioned to this alternative, TAK-243-compatible anticoagulation agent

Who cannot join

  • Patients who are receiving any other investigational agents
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
  • Life-threatening illness unrelated to cancer
  • Patients with uncontrolled coagulopathy or bleeding disorder
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Known cardiopulmonary disease defined as:
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  • Unstable angina pectoris;
  • Congestive heart failure (New York Heart Association [NYHA] class III or IV);
  • Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a [acute coronary syndrome (ACS)], MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);
  • Cardiomyopathy
  • Clinically significant arrhythmia:
  • History of polymorphic ventricular fibrillation or torsade de pointes,
  • Permanent atrial fibrillation (a fib), defined as continuous a fib for >= 6 months,
  • Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening,
  • Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker) or ablation, and
  • Patients with paroxysmal a fib or < grade 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen
  • Prolonged rate corrected QT (QTc) interval >= 470 m/sec, calculated according to institutional guidelines
  • Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
  • Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis
  • Major surgery within 14 days before the first dose of any study drug
  • Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s)
  • Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s)
  • Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for >= 1 month after treatment of the brain metastases. Patients on anti-seizure medications may be enrolled at the discretion of the principal investigator
  • TAK-243 is primarily metabolized by CYP3A4/5. Therefore, the concomitant use of strong inhibitors of CYP3A4/5 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) and strong inducers of CYP3A4/5 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) is not permitted from 14 days prior to enrollment until the end of the study
  • TAK-243 is a substrate for both organic anion transporting polypeptides (OATP) in human hepatocytes and the drug efflux transporter BCRP (ABCG2). Therefore, concomitant use of drugs that are strong inhibitors of BCRP or OATP is not permitted from 14 days prior to enrollment until the end of the study
  • Other medications that are prohibited while on TAK-243 treatment include herbal medications/preparations (except for vitamins). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of
  • As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients undergoing vaccination with live vaccines and live attenuated vaccines in the 30 days prior to receiving TAK-243, during the study, and for 100 days after the last dose of study drug. Inactivated vaccines are permitted
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243
  • Patients with evidence of chronic hepatitis B virus (HBV) infection who are currently on treatment are eligible if they have an undetectable HBV viral load
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Known human immunodeficiency virus (HIV)-positive patients who meet the following criteria will be considered eligible:
  • CD4 count > 350 cells/mm^3
  • Undetectable viral load for 6 months prior to enrollment
  • Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents
  • No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections
  • Pregnant and lactating/breast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892

    Site Public Contact, 800-411-1222

    Sarah Shin

    Recruiting

Other trials in United States

About this study

Official title: A Phase I Study to Investigate the Safety of the Ubiquitin Activating Enzyme Inhibitor TAK-243 in Adult Solid Tumor and Lymphoma Patients

This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) and in patients with lymphoma. TAK-243 is a drug that binds to and inhibits the ubiquitin-activating enzyme, an enzyme that is more active on cancer cells than healthy cells, inhibiting tumor cell proliferation and survival.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To establish the safety, tolerability, and the recommended phase II dose of UAE inhibitor TAK-243 (TAK-243) administered twice-weekly or once-weekly in patients with advanced solid tumors and lymphomas.

SECONDARY OBJECTIVES:

  1. To evaluate the pharmacokinetic (PK) profiles of TAK-243 administered on twice-weekly and once-weekly schedules in patients with advanced solid tumors and lymphomas.

II. To determine the effects of TAK-243 on levels of K48-linked ubiquitination in pre- and post-treatment tumor biopsies.

III. To observe and record anti-tumor activity.

EXPLORATORY OBJECTIVES:

  1. To determine the effects of TAK-243 on the endoplasmic reticulum (ER) stress marker CHOP, Mcl-1-Noxa heterodimer formation, and the apoptosis marker cleaved caspase-3 in pre- and post-treatment tumor biopsies II. To evaluate potential associations between TAK-243 activity and tumor genomic alterations or ribonucleic acid (RNA) expression profiles.

III. To preliminarily assess progression-free survival (PFS) and overall survival (OS) for TAK-243 monotherapy in patients with advanced solid tumors and lymphomas.

OUTLINE: This is a dose-escalation study of TAK-243 followed by a dose-expansion study. Patients are assigned to 1 of 2 arms.

ARM A: Patients receive UAE inhibitor TAK-243 intravenously (IV) on days 1, 4, 8, and 11 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo computed tomography (CT), magnetic resonance imaging (MRI), and collection of blood throughout the study, and may undergo echocardiograms (ECHO) as clinically indicated on study.

ARM B: Patients receive UAE inhibitor TAK-243 IV once weekly (QW) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo CT, MRI, and collection of blood throughout the study, and may undergo ECHO as clinically indicated on study.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • UAE Inhibitor TAK-243Drug

    Also called AOB87172, MLN7243, TAK-243

    Given IV

Study groups in NCT06223542
Study groupRoleWhat they receive
Arm A (twice weekly UAE inhibitor TAK-243)ExperimentalPatients receive UAE inhibitor TAK-243 IV on days 1, 4, 8, and 11 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo CT, MRI, and collection of blood throughout the study, and may undergo ECHO as clinically indicated on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Drug: UAE Inhibitor TAK-243
Arm B (once weekly UAE inhibitor TAK-243)ExperimentalPatients receive UAE inhibitor TAK-243 IV on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy on study, and undergo CT, MRI, and collection of blood throughout the study, and may undergo ECHO as clinically indicated on study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Drug: UAE Inhibitor TAK-243

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)

    The MTD for each arm will be based on the assessment of dose-limiting toxicities (DLTs) and will be defined as the dose level at which less than one-third of patients (< 2/6 patients) treated at that dose experience a DLT, with the next higher dose level demonstrating a one-third or greater number of patients (>= 2/3 or >= 2/6 patients) having DLT.

    Measured: Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

  2. Recommended phase 2 dose

    Measured: Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

  3. Incidence of DLTs

    A DLT is defined as an adverse event that is felt to be related (possibly, probably, or definitely) to administration of study drugs, and meets pre-specified criteria. All toxicities will be reported for all patients who receive any amount of study drug on this study.

    Measured: Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)

Secondary outcomes (2)

  1. Pharmacodynamic (PD) variables

    With 10 PD sample pairs, there is 90% power to detect a treatment effect equivalent to 1.8 standard deviations (associated with the inter-patient baseline variability of the PD marker) with the paired 2-sample t-test, at the 1-sided .01 significance level (to accommodate multiple endpoints while maintaining a reasonable over-all type 1 error bound), for a given PD variable of interest. PD variables may be log-transformed to achieve more nearly normal distributions.

    Measured: Up to 30 days after the last dose of treatment

  2. Objective tumor response

    For each of the two administration schedule arms, the objective tumor response rate will be estimated for the entire patient population in a descriptive fashion, including a 2-sided 90% confidence interval.

    Measured: Up to 30 days after the last dose of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2024
  2. Study start24 Mar 2025
  3. Primary completion15 Apr 2027 (estimated)
  4. Study completion15 Apr 2027 (estimated)

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06223542
Sponsor's protocol ID
NCI-2022-11194
Other IDs
NCI-2022-11194, 10299, 10299
Status last verified
Oct 2026
First submitted
24 Jan 2024
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.

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 25 inclusion and 37 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: Within the first cycle of treatment (Arm A: 21-day cycle; Arm B: 28-day cycle)). The study lists 3 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 NCT06223542.

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 13 Oct 2026.

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