Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL

November 17, 2023 updated by: Kymera Therapeutics, Inc.

A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, PK/PD, and Clinical Activity of Intravenously Administered KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL

This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in patients with R/R NHL. The Phase 1a stage of the study will explore escalating doses of single-agent KT-413. The Phase 1b stage will be split into 2 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in MYD88 mutant and MYD88 wild-type R/R DLBCL.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom
        • University College London Hospitals
      • Southampton, United Kingdom
        • University Hospital Southampton NHS Foundation Trust
  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Phase 1a Only:

    • Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health Organization (WHO) classification. Diffuse large B-cell lymphoma (DLBCL) includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; human herpesvirus 8 (HHV8) positive DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type. Patients with indolent lymphoma are eligible if they meet criteria for systemic treatment.
    • Clinicopathological diagnosis of Waldenström's Macroglobulinemia (WM) based on the consensus panel criteria from the Second International Workshop on WM

    • Histologically/cytologically confirmed relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL) by cerebrospinal fluid (CSF) or biopsy. PCNSL patients are considered eligible if the Investigator believes that there is no other reasonable treatment alternative.

      • Note: Patients with HIV-associated PCNSL are not eligible.
      • Note: Patients with secondary CNS metastases are eligible assuming they meet other study criteria. Patients with secondary CNS metastases include those who have synchronous systemic and CNS involvement or those who have been previously treated and relapsed with isolated CNS involvement.
  • Phase 1b Only: Histologically confirmed diagnosis of DLBCL according to the 2016 WHO classification including: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; HHV8+ DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type.
  • Disease relapsed and/or refractory to at least 2 accepted standard systemic regimens for all indications except PCNSL. For PCNSL, patients must be relapsed and/or refractory to at least 1 prior regimen.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening.
  • Adequate organ and bone marrow function, in the absence of growth factors
  • Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol

Exclusion Criteria:

  • Infection with hepatitis B (HBV), hepatitis C (HCV), or active viral infection with human immunodeficiency virus (HIV).
  • Radiation treatment within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
  • Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
  • Ongoing unstable cardiovascular function including history of myocardial infarction within 3 months of planned start of study drug.
  • Patient has not recovered from any clinically significant AEs of previous treatments to pre-treatment baseline or Grade 1 prior to first dose of study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1a Dose Escalation
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.
Experimental: Phase 1b Dose Expansion MYD88MT
KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 mutant DLBCL.
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.
Experimental: Phase 1b Dose Expansion MYD88WT
KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 wild type DLBCL.
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To establish the Maximum Tolerated Dose (MTD)
Time Frame: Within first 3 weeks of treatment
Phase 1a
Within first 3 weeks of treatment
Number of Participants with protocol specified Dose Limiting Toxicities (DLTs)
Time Frame: Within first 3 weeks of treatment
Phase 1a
Within first 3 weeks of treatment
Dose recommended for future studies
Time Frame: Within first 3 weeks of treatment
Phase 1a/1b
Within first 3 weeks of treatment
Clinical Laboratory Abnormalities
Time Frame: Clinical laboratory abnormalities 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)
Clinical laboratory abnormalities will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy
Adverse Event Parameters
Time Frame: Adverse Event Parameters 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)
Adverse Event Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy
ECG Parameters
Time Frame: ECG Parameters 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
ECG Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration versus time curve for KT-413 from time zero to last quantifiable time point (AUC0-t)
Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Phase 1a/1b
Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Maximum Plasma Concentration of KT-413 (Cmax)
Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Phase 1a/1b
Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Time of maximum plasma concentration of KT-413 (Tmax)
Time Frame: Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Phase 1a/1b
Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Half-life of KT-413 [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 21 days)
Phase 1a/1b
Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Amount of KT-413 excreted in urine from time zero to last collected timepoint (Ae0-t)
Time Frame: Urine samples for PK analysis collected during the first cycle (21 day cycle)
Phase 1a/1b
Urine samples for PK analysis collected during the first cycle (21 day cycle)
Evidence of clinical activity of KT-413 as determined by Objective Response Rate (ORR)
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
Phase 1a/1b
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
Duration of Response (DOR) as assessed by the Investigator
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
Phase 1a/1b
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
Progression-free survival (PFS) as assessed by the Investigator
Time Frame: From time of entry on study through progression, up to 18 months
Phase 1b
From time of entry on study through progression, up to 18 months
Disease Control Rate (DCR) as assessed by the investigator
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
Phase 1b
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
Overall Survival (OS) as assessed by the investigator
Time Frame: From time of entry on study through death or date last known alive at end of follow-up, up to 18 months
Phase 1b
From time of entry on study through death or date last known alive at end of follow-up, up to 18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
KT-413 levels in peripheral blood mononuclear cells
Time Frame: Blood samples for PD analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)
Phase 1a/1b
Blood samples for PD analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kymera Therapeutics, Inc.

Investigators

  • Study Director: Ashwin Gollerkeri, MD, Kymera Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2022

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

January 18, 2022

First Submitted That Met QC Criteria

January 31, 2022

First Posted (Actual)

February 10, 2022

Study Record Updates

Last Update Posted (Estimated)

November 21, 2023

Last Update Submitted That Met QC Criteria

November 17, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KT413-DL-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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