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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05225584
Recruitment Status : Recruiting
First Posted : February 4, 2022
Last Update Posted : August 10, 2022
Sponsor:
Information provided by (Responsible Party):
Kymera Therapeutics, Inc.

Brief 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 Lymphomas, Large Granular Lymphocytic Leukemia, 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), Large Granular Lymphocytic Leukemia (LGL-L), and solid tumors.

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma (NHL) Peripheral T-cell Lymphoma (PTCL) Cutaneous T-Cell Lymphoma (CTCL) Large Granular Lymphocytic Leukemia (LGL-L) Solid Tumors Drug: KT-333 Phase 1

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 and solid tumors will be enrolled in Phase 1a. Phase 1b will consist of separate cohorts of patients with R/R Peripheral T-cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Large Granular Lymphocytic Leukemia (LGL-L), and solid tumors.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Open-Label, Dose-Escalation/Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Clinical Activity of Intravenous KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, and Solid Tumor
Actual Study Start Date : January 5, 2022
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : March 2025


Arm Intervention/treatment
Experimental: Phase 1a Dose Escalation Lymphomas
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Experimental: Phase 1a Dose Escalation Solid Tumors
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Experimental: Phase 1b Dose Expansion PTCL
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Experimental: Phase 1b Dose Expansion CTCL
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Experimental: Phase 1b Dose Expansion LGLL
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Experimental: Phase 1b Dose Expansion Solid Tumor
KT-333 dosed IV weekly in 28 day cycles
Drug: KT-333
KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.




Primary Outcome Measures :
  1. 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 ]
    Incidence and severity of adverse events as assessed by CTCAE v5.0 Phase 1a/1b

  2. 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 ]
    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

  3. 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 ]
    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

  4. Maximum Tolerated Dose (MTD) [ Time Frame: Within the first 28 days of treatment ]
    To establish the Maximum Tolerated Dose (MTD) Phase 1a

  5. Dose Limiting Toxicities (DLTs) [ Time Frame: Within the first 28days of treatment ]
    Number of Participants with protocol specified Dose Limiting Toxicities (DLTs) Phase 1a


Secondary Outcome Measures :
  1. Area under the plasma concentration versus time curve for KT-333 [ Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days) ]
    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

  2. Maximum Plasma Concentration of KT-333 (Cmax) [ Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days) ]
    Maximum Plasma Concentration of KT-333 (Cmax)

  3. Time of maximum plasma concentration of KT-333 (Tmax) [ Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days) ]
    Time of maximum plasma concentration of KT-333 (Tmax) Phase 1a/1b

  4. Half-life of KT-333 if data permits (T1/2) [ Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days) ]
    Half-life of KT-333 if data permits (T1/2) Phase 1a/1b

  5. Amount of KT-333 dose excreted in urine from time zero to last collected time point (Ae0-t) [ Time Frame: Urine samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days) ]
    Amount of KT-333 dose excreted in urine from time zero to last collected time point (Ae0-t) Phase 1a

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

  7. Evidence of clinical activity of KT-333 [ Time Frame: 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 ]
    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.

  8. Evidence of clinical activity of KT-333 [ Time Frame: 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 ]
    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

  9. Evidence of clinical activity of KT-333 [ Time Frame: 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 ]
    Evidence of clinical activity of KT-333 as determined by ORR by hematologic response Phase 1b only

  10. Duration of Response (DOR) [ Time Frame: From date of first of response to the date of documented first progression or death whichever comes first, about 18 months ]
    Duration of Response (DOR) Phase 1a/1b



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Phase 1a Only: Histologically or pathologically confirmed Lymphomas (including Hodgkin's, B-cell, T-cell, Small Lymphocytic, or NK-cell Lymphomas) and solid tumors with the exception of chronic lymphocytic leukemia (CLL) Note: Patients with indolent 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.
  2. 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.
  3. Fresh or archival formalin fixed paraffin embedded (FFPE) tumor tissue or 15 slides preferably collected within 6 months prior to first dose of the study drug (for lymphoma patients) or within 2 years prior to first dose of the study drug (for solid tumor patients). .
  4. Phase 1a only: Relapsed and/or refractory disease to at least 2 prior systemic standard of care treatments or for whom standard therapies are not available.
  5. Phase 1b only: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatments or for whom standard therapies are not available.
  6. LGL-L patients only:

    • Severe neutropenia < 500/mm3, or,
    • Neutropenia associated with recurrent infection, or,
    • Symptomatic anemia and/or,
    • Transfusion-dependent anemia.
  7. PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patients with non-measurable disease are allowed in Phase1a
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).
  9. 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.

Exclusion Criteria:

  1. History or suspicion of central nervous system (CNS) metastases.
  2. History of or active concurrent malignancy other than lymphoma or solid tumors unless the patient has been disease-free for ≥ 2 years.
  3. 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.
  4. Ongoing unstable cardiovascular function.
  5. Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.
  6. Prior allogenic hematopoietic or bone marrow transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05225584


Contacts
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Contact: Rachelle Perea 619-804-9472 rperea@kymeratx.com

Locations
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United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
Contact: Dana Haycraft    502-899-3366    dana.haycraft@nortonhealthcare.org   
United States, New Jersey
Hackensack University Medical Center, John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Elizabeth McCarthy, MSN, RN    412-860-6447    elizabethl.mccarthy@hmhn.org   
United States, New York
Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10467
Contact: Joel Victor    718-920-6680    jovictor@montefiore.org   
United States, Ohio
The Christ Hospital Cancer Center Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Abby Reed    513-585-1140    abby.reed@thechristhospital.com   
United States, Pennsylvania
Thomas Jefferson University, Sidney Kimmel Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Pierluigi Porcu, MD    215-586-0199    askphase1@jefferson.edu   
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Auris Huen, MD    713-745-1113    aohuen@mdanderson.org   
Contact: Jasmine Leung, RN, BSN    713-794-1453    JCLeung@mdanderson.org   
United States, Washington
University of WA/Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98195
Contact: Stephen Smith, MD    206-606-6546    ssmith50@seattlecca.org   
Sponsors and Collaborators
Kymera Therapeutics, Inc.
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Responsible Party: Kymera Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05225584    
Other Study ID Numbers: KT333-TL-101
First Posted: February 4, 2022    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Leukemia, Large Granular Lymphocytic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, T-Cell