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Non Hodgkin Lymphoma (NHL)Phase 1NCT05225584

Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors

A Phase 1 study testing KT-333 in people with Non Hodgkin Lymphoma (NHL) and Peripheral T-cell Lymphoma (PTCL), run by Kymera Therapeutics, Inc. at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of KT-333 in Adult patients with Relapsed or Refractory (R/R) Lymphomas, Large Granular Lymphocytic Leukemia (LGL-L), T-cell prolymphocytic leukemia (T-PLL), and Solid Tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
KT-333
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
13 sitesUnited States
Study dates
19 May 2022to 3 Mar 2025
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Phase 1a Only: Cytologically or pathologically confirmed Lymphomas (including Hodgkin's, B-cell, T-cell, Small Lymphocytic, or Natural-Killer (NK)-cell Lymphomas and LGL-L), T-PLL and solid tumors with the exception of chronic lymphocytic leukemia (CLL) Note: Patients with indolent non-Hodgkin's lymphoma (NHL) and small lymphocytic lymphoma (SLL) are only eligible if not require immediate cytoreductive therapy or if there are no available treatments with potential benefit.
  • Phase 1b Only: Histologically or pathologically confirmed PTCL, CTCL, LGL-L [T-cell LGL-L or Chronic Lymphoproliferative Disorder of NK-cells (CLPD-NK)], or solid tumors.
  • Fresh or archival formalin fixed paraffin embedded (FFPE) tumor tissue or 15 slides preferably collected within 6 months or 2 years prior to first dose of the study drug (for lymphoma and solid tumor patients respectively).
  • Phase 1a only: Lymphoma and Solid Tumor: Relapsed and/or refractory disease to at least 2 prior systemic standard of care treatments or for whom standard therapies are not available.
  • Phase 1a: LGL-L/T-PLL only: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatment or for whom standard therapies are not available.
  • Phase 1b only: All disease types: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatments or for whom standard therapies are not available.
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  • LGL-L patients only (hematology specific criteria):
  • One of the following:
  • Severe neutropenia < 500/mm3, or,
  • Symptomatic anemia and/or,
  • Transfusion-dependent anemia.
  • ANC ≥ 200/μL at Screening and C1D1 (pre dose)
  • Platelet count ≥ 100,000/μL (assessed ≥ 7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets).
  • LGL-L Patients Only (baseline disease characteristics):
  • CD3+CD8+ cell population >650/mm3;
  • CD3+CD8+CD57+ population >500/mm3;
  • Presence of a clonal T-cell receptor (within 1 month of diagnosis);
  • Note: patients with T-LGLL may be included with PI approval even if CD3+CD8+ cell population is<650/mm3 or CD3+CD8+CD57+ population is <500/mm3, though +TCR is required;
  • NK LGL is also permitted, provided there is a clonal NK-cell population noted with>500 cells/mm3
  • PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patients with non-measurable disease are allowed in Phase1a
  • T-PLL: Measurable disease per Lugano and/or atypical T lymphocytes quantifiable by flow cytometry or morphology in the peripheral blood or bone marrow.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).
  • Adequate bone marrow function at Screening and C1D1 (pre-dose) for all patients except those with LGL-L Adequate liver/kidney organ function at Screening and C1D1 (pre-dose) for all patients.
  • Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive methods for the duration of study treatment and 6 months after the last dose of KT333.

Who cannot join

  • Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
  • Note: Patients with solid tumors are eligible if their CNS metastases or cord compression have been treated (e.g., radiotherapy, stereotactic surgery) and they are clinically stable, off steroids for at least 4 weeks before first dose of study drug and have no evidence of progression at time of study enrollment.
  • Note: Patients with lymphomas are eligible if their CNS metastases or cord compression have been treated effectively (i.e. achieved CR) and there is no clinical or radiographic evidence of active lymphoma.
  • Diagnosis of Chronic Lymphocytic Leukemia (CLL).
  • History of or active concurrent malignancy other than lymphoma or solid tumors unless the patient has been disease-free for ≥ 2 years.
  • Patient has not recovered from any clinically significant adverse events (AEs) of previous treatments to pretreatment baseline or Grade 1 prior to first dose of study drug.
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  • Ongoing unstable cardiovascular function.
  • Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.
  • Prior allogenic hematopoietic or bone marrow transplant.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • University of Virginia, Emily Couric Cancer Center

    Charlottesville, Virginia, 22903

  • The Christ Hospital Cancer Center

    Cincinnati, Ohio, 45219

  • Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210-1240

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Hackensack University Medical Center, John Theurer Cancer Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Norton Cancer Institute

    Louisville, Kentucky, 40207

  • UC Irvine Health-Chao Family Comprehensive Cancer Center

    Orange, California, 92868-3201

  • Abramson Cancer Center of the University of Pennsylvania Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University, Sidney Kimmel Cancer Center

    Philadelphia, Pennsylvania, 19107

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • University of WA/Seattle Cancer Care Alliance

    Seattle, Washington, 98195

  • Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered KT-333 in Adult Patients With Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia, and Solid Tumors

This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of KT-333 in Adult patients with Relapsed or Refractory (R/R) Lymphomas, Large Granular Lymphocytic Leukemia (LGL-L), T-cell prolymphocytic leukemia (T-PLL), and Solid Tumors. The Phase 1a stage of the study will explore escalating doses of single-agent KT-333. The Phase Ib stage will consist of 4 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of KT-333 in Peripheral T-cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), LGL-L, and solid tumors.

Read the detailed description

This is an open-label Phase 1a (dose escalation)/1b (dose expansion) first-in-human study of KT-333 in adult patients. Patients with relapsed/refractory (R/R) lymphomas, LGL-L, T-PLL, and solid tumors will be enrolled in Phase 1a. Phase 1b will consist of separate cohorts of patients with R/R PTCL, CTCL, LGL-L, and solid tumors.

Being tested
KT-333
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell, Cutaneous, Leukemia, Large Granular Lymphocytic, Leukemia, Prolymphocytic, T-Cell

What participants receive

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

  • KT-333Drug

    KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Study groups in NCT05225584
Study groupRoleWhat they receive
Phase 1a Dose Escalation LymphomasExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1a Dose Escalation Solid TumorsExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1b Dose Expansion PTCLExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1b Dose Expansion CTCLExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1b Dose Expansion LGL-LExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1b Dose Expansion Solid TumorExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1a Dose Escalation LGL-LExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333
Phase 1a Dose Escalation T-PLLExperimentalKT-333 dosed IV weekly in 28 day cycles
Receives: Drug: KT-333

What is being measured

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

  1. Safety

    Incidence and severity of adverse events as assessed by CTCAE v5.0 Phase 1a/1b

    Measured: Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

  2. Safety

    Incidence and severity of clinical laboratory abnormalities in Serum Chemistry, Hematology, Coagulation Parameters and urinalysis tests as assessed by CTCAE v5.0 Phase 1a/1b

    Measured: Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

  3. Safety

    Changes in the ECG parameters, including heart rate and measures PR, QRS, QT, and QTc intervals as assessed by CTCAE v5.0 Phase 1a/1b

    Measured: Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

  4. Maximum Tolerated Dose (MTD)

    To establish the Maximum Tolerated Dose (MTD) Phase 1a

    Measured: Within the first 28 days of treatment

  5. Dose Limiting Toxicities (DLTs)

    Number of Participants with protocol specified Dose Limiting Toxicities (DLTs) Phase 1a

    Measured: Within the first 28days of treatment

Secondary outcomes (11)

  1. Area under the plasma concentration versus time curve for KT-333

    Area under the plasma concentration versus time curve for KT-333 from time to zero to last quantifiable time point (AUC 0-t ) Phase 1a/1b

    Measured: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

  2. Maximum Plasma Concentration of KT-333 (Cmax)

    Maximum Plasma Concentration of KT-333 (Cmax)

    Measured: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

  3. Time of maximum plasma concentration of KT-333 (Tmax)

    Time of maximum plasma concentration of KT-333 (Tmax) Phase 1a/1b

    Measured: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

  4. Half-life of KT-333 if data permits (T1/2)

    Half-life of KT-333 if data permits (T1/2) Phase 1a/1b

    Measured: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

  5. Amount of KT-333 dose excreted in urine from time zero to last collected time point (Ae0-t)

    Amount of KT-333 dose excreted in urine from time zero to last collected time point (Ae0-t) Phase 1a

    Measured: Urine samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

  6. Evidence of clinical activity of KT-333

    Evidence of clinical activity of KT-333 as determined by Objective Response Rate (ORR) as per Lugano criteria 2014 for Lymphomas Phase 1a/1b.

    Measured: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

  7. Evidence of clinical activity of KT-333

    Evidence of clinical activity of KT-333 as determined by RECIST 1.1 to determine ORR , complete response (CR), partial response (PR) for solid tumors Phase 1a/1b.

    Measured: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

  8. Evidence of clinical activity of KT-333

    Evidence of clinical activity of KT-333 as determined by ORR by Modified Severity-Weighted Assessment Tool (mSWAT) for Cutaneous T-Cell Lymphoma (CTCL) Phase 1a/1b

    Measured: Composite assessment from date of baseline assessment until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

  9. Evidence of clinical activity of KT-333

    Evidence of clinical activity of KT-333 as determined by ORR by investigator assessment for Large Granular Lymphocytic Leukemia (LGL-L) Phase 1a/1b

    Measured: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

  10. Evidence of clinical activity of KT-333

    Evidence of clinical activity of KT-333 as determined by ORR based on T-PLL International Study Group criteria, Phase 1a

    Measured: From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months

  11. Duration of Response (DOR)

    Duration of Response (DOR) Phase 1a/1b

    Measured: From date of first of response to the date of documented first progression or death whichever comes first, about 18 months

Timeline

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

  1. First posted4 Feb 2022
  2. Study start19 May 2022
  3. Primary completion3 Mar 2025
  4. Study completion3 Mar 2025

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
Sequential
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05225584
Sponsor's protocol ID
KT333-TL-101
Status last verified
Mar 2025
First submitted
16 Dec 2021
Last updated
19 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KT-333 in people with Non Hodgkin Lymphoma (NHL) and Peripheral T-cell Lymphoma (PTCL), run by Kymera Therapeutics, Inc. at 13 sites 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 24 inclusion and 9 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 19 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety (time frame: Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy). The study lists 5 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 NCT05225584.

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 19 Mar 2025.

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