A First-in-Human Study of KK2223 in Participants With Relapsed or Refractory T Cell Non-Hodgkin Lymphoma

Официальное название

A Phase 1, Multicenter, Open-label, Non-randomized, Dose-escalation and Backfill Study of KK2223 in Participants With Relapsed or Refractory T-cell Non Hodgkin Lymphoma

Обзор

The purpose of this study is to determine the safety, tolerability, PK and pharmacodynamics of KK2223 in adult participants with relapsed or refractory peripheral T cell lymphoma (PTCL) or cutaneous T cell lymphoma (CTCL).

Подробное описание

This is a Phase 1, multicenter, open-label, non randomized study in participants with relapsed or refractory PTCL or CTCL. This study consists of Part 1 (dose-escalation) and Part 2 (backfill). The purpose of this study is to determine the safety, tolerability, PK and pharmacodynamics of K2223 in r/r T-cell NHL (PTCL or CTCL)

Вмешательства

• Препарат KK2223
  Intravenous infusion

Первичные конечные точки

• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]
• Assess the incidence of treatment-emergent adverse events and determine the maximum tolerated dose (MTD) of KK2223 in patients with relapsed or refractory peripheral or cutaneous T cell lymphoma (PTCL/CTCL). [Срок оценки: Through study completion, an average of 1.5 years]

Вторичные конечные точки (12)

• Mean Blood Drug Concentration [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the immunogenicity of KK2223. [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). [Срок оценки: Through study completion, an average of 1.5 years]
• To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). [Срок оценки: Through study completion, an average of 1.5 years]
• Pharmacokinetic Parameter Maximum Blood Concentration (Cmax) [Срок оценки: Through study completion, an average of 1.5 years]
• Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) [Срок оценки: Through study completion, an average of 1.5 years]
• Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) [Срок оценки: Through study completion, an average of 1.5 years]
• Pharmacokinetic Parameter Terminal Half-Life (Thalf) [Срок оценки: Through study completion, an average of 1.5 years]
• Pharmacokinetic Parameter Clearance (CL) [Срок оценки: Through study completion, an average of 1.5 years]

Критерии участия

Критерии включения

• Adults (≥18 years) with confirmed T-cell lymphoma subtypes: PTCL (including nodal T-follicular helper cell lymphoma, ALCL, PTCL NOS) for Parts 1 and 2; CTCL (mycosis fungoides or Sézary syndrome, stages IIB-IV) for Parts 1 and 2, with specific disease involvement criteria in Part 2.
• PTCL participants must have relapsed/refractory/intolerant to ≥1 systemic therapy; CD30+ PTCL must have prior brentuximab vedotin treatment or intolerance, and/or ALK-positive ALCL participants should have previously received crizotinib if indicated (crizotinib administration is applicable to US sites only). CTCL participants must have relapsed/refractory/intolerant to ≥2 systemic therapies.
• Availability of tumor tissue (current or archival) is required.
• Measurable disease required: nodal/extranodal lesions for PTCL and assessable skin disease for CTCL.
• ECOG performance status 0-1; adequate neutrophils (≥1000/µL), platelets (≥75,000/µL), renal function (creatinine clearance ≥60 mL/min), liver function within defined limits, and total bilirubin ≤1.5× ULN (up to 3× ULN with Gilbert's syndrome).
• Body weight 40 kg to ≤ 200 kg
• Life expectancy ≥3 months.
• Negative pregnancy test for females of childbearing potential; contraception required for females and males with partners of childbearing potential during and after treatment.
• Restrictions on gamete donation and freezing during and after treatment.
• Ability to provide informed consent and comply with study procedures. -

Критерии исключения

• Recent autologous or allogeneic transplant within 120 days before treatment; active GVHD or ongoing immunosuppression after allogeneic transplant; prior HSCT and with active VOD/SOS
• Pregnant or breastfeeding females, or those intending pregnancy.
• History of HIV, HBV, or HCV infections generally excluded, except for controlled or resolved cases as defined.
• Uncontrolled infections requiring antibiotics, antivirals, or antifungals at screening through treatment start.
• Significant medical history or complications within six months prior to enrollment, including advanced congestive heart failure (NYHA Class III or higher), recent unstable angina or myocardial infarction, autoimmune diseases requiring systemic immunosuppressive therapy, active or uncontrolled ocular diseases, Grade 3 or 4 peripheral neuropathy, or other poorly controlled conditions as judged by the investigator (e.g., uncontrolled hypertension, diabetes, or arrhythmias).
• Use of other investigational drugs within 14 days or 5 half-lives before treatment.
• Steroid use over 10 mg/day prednisone equivalent within 14 days prior, except limited corticosteroid use with specific tapering guidelines; topical steroids allowed under conditions for CTCL.
• Major surgery, radiotherapy, chemotherapy, or other anti-cancer treatments within 14 days or 5 half-lives before treatment.
• Prior mogamulizumab use within six months before treatment; associated rash must be ruled out if >6 months.
• Known history of Grade ≥ 3 hypersensitivity to mogamulizumab.
• Failure to recover from prior non-hematologic toxicities to Grade 0 or 1 (except alopecia and mild neuropathy).
• Prolonged QT/QTc interval (e.g., QTcF >480 ms).
• Active second primary malignancies except specified non-exclusionary cases.
• CNS involvement.
• Any condition that may impair compliance or study completion as judged by the Investigator.
• Known hypersensitivity to any excipients in the drug formulation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• University of California, Irvine Medical Center - Hematology/Oncology — Orange
• Stanford University School of Medicine — Stanford
• Beth Israel Deaconess Medical Center - Research — Boston
• Washington University School of Medicine - Oncology Hospital - Public — St Louis
• Hackensack University Medical Center - John Theurer Cancer C - Lymphoma Division — Hackensack
• Memorial Sloan Kettering Cancer Center — New York
• Oregon Health & Science University — Portland
• University of Pennsylvania - Abramson Cancer Center — Philadelphia
• … и ещё 1 центр

Италия · 4 центра

• Istituto di Candiolo, IRCCS - Oncologia Medica ed Ematologia — Candiolo
• Azienda Ospedaliera Papa Giovanni XXIII - Ematologia — Bergamo
• Azienda Ospedaliero Universitaria di Bologna IRCCS (Policlinico di Sant'Orsola) - Ematolog — Bologna
• AOU Citta' della Salute e della Scienza di Torino Ospedale Molinette, Ematologia Universit — Torino

Испания · 4 центра

• Hospital Clinic De Barcelona - Hematología — Badalona
• Institut Català d'Oncologia (ICO) - ICO L'Hospitalet - Hematologia — L'Hospitalet de Llobregat
• Clinica Universidad de Navarra - Hematología — Pamplona
• Clinica Universidad de Navarra - Hematología y Hemoterapia — Madrid

Идентификаторы

NCT: NCT07192471 · 2223-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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