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

NCT05233033 | Completed Phase 1 FDA Drug

• 1 other identifier: KT413-DL-101
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; DLBCL; MYD88 Gene Mutation

Outcome Measures

Primary Outcomes (6)

• To establish the Maximum Tolerated Dose (MTD)

  Phase 1a

  Within first 3 weeks of treatment

• Number of Participants with protocol specified Dose Limiting Toxicities (DLTs)

  Phase 1a

  Within first 3 weeks of treatment

• Dose recommended for future studies

  Phase 1a/1b

  Within first 3 weeks of treatment

• Clinical Laboratory Abnormalities

  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

  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

  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 Outcomes (10)

• Area under the plasma concentration versus time curve for KT-413 from time zero to last quantifiable time point (AUC0-t)

  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)

  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)

  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)]

  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)

  Urine samples for PK analysis collected during the first cycle (21 day cycle)

Other Outcomes (1)

• KT-413 levels in peripheral blood mononuclear cells

  Blood samples for PD analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)

Study Arms (3)

Phase 1a Dose Escalation

EXPERIMENTAL

Drug: KT-413

Phase 1b Dose Expansion MYD88MT

EXPERIMENTAL

KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 mutant DLBCL.

Drug: KT-413

Phase 1b Dose Expansion MYD88WT

EXPERIMENTAL

KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 wild type DLBCL.

Drug: KT-413

Interventions

KT-413 DRUG

KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.

Phase 1a Dose Escalation; Phase 1b Dose Expansion MYD88MT; Phase 1b Dose Expansion MYD88WT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kymera Therapeutics, Inc.: lead

Study Sites (8)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

University College London Hospitals

London, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Study Officials

• Ashwin Gollerkeri, MD

  Kymera Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 10, 2022
• Study Start: June 13, 2022
• Primary Completion: July 28, 2023
• Study Completion: July 28, 2023
• Last Updated: December 10, 2024

Record last verified: 2024-12

Locations

GB (2); US (6)