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

• ClinicalTrials.gov Identifier: NCT05233033
• Recruitment Status: Recruiting
• First Posted: February 10, 2022
• Last Update Posted: May 12, 2023
• Sponsor: Kymera Therapeutics, Inc.
• Information provided by (Responsible Party): Kymera Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; DLBCL; MYD88 Gene Mutation	Drug: KT-413	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 13, 2022
• Estimated Primary Completion Date: April 2025
• Estimated Study Completion Date: May 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. To establish the Maximum Tolerated Dose (MTD) [ Time Frame: Within first 3 weeks of treatment ]
   Phase 1a
2. Number of Participants with protocol specified Dose Limiting Toxicities (DLTs) [ Time Frame: Within first 3 weeks of treatment ]
   Phase 1a
3. Dose recommended for future studies [ Time Frame: Within first 3 weeks of treatment ]
   Phase 1a/1b
4. 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)
5. 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)
6. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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

Other Outcome Measures:

1. 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, District of Columbia

MedStar Georgetown University Hospital; Recruiting

Washington, District of Columbia, United States, 20007

Contact: Monica Rengifo Pardo 202-687-6957 mr1792@georgetown.edu

United States, Kentucky

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40207

Contact: Don Stevens 502-899-3366 HEME-NCIResearch@nortonhealthcare.org

United States, Michigan

Henry Ford Health System; Recruiting

Detroit, Michigan, United States, 48202

Contact: Cesar Figueras, RN 313-556-8731 cfiguer1@hfhs.org

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Jennifer Lue, MD 646-608-4160 LueJ@mskcc.org

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Chizobam Obi 713-794-3074 ciobi@mdanderson.org

United States, Virginia

University of Virginia Comprehensive Cancer Center; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Erica Stallard 434-243-2649 elg9r@hscmail.mcc.virginia.edu

Sponsors and Collaborators

Kymera Therapeutics, Inc.

Investigators

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

More Information

• Responsible Party: Kymera Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05233033
• Other Study ID Numbers: KT413-DL-101
• First Posted: February 10, 2022
• Last Update Posted: May 12, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell