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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: T-cell NHL (PTCL or CTCL)
• Intervention / Treatment: Drug: KK2223

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kyowa Kirin, Inc.; Phone Number: +1-609-919-1100; Email: KKD.Clinical.82@kyowakirin.com

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII - Ematologia
    • Principal Investigator: Giuseppe Gritti
    • Contact: Giuseppe Gritti; Phone Number: 39035269492; Email: giuseppe_gritti@yahoo.it
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna IRCCS (Policlinico di Sant'Orsola) - Ematologia
    • Contact: Luigi Zinzani Pier; Phone Number: 390516363680; Email: pierluigi.zinzani@unibo.it
    • Principal Investigator: Luigi Zinzani Pier
  • Torino, Italy, 10126
    • AOU Citta' della Salute e della Scienza di Torino Ospedale Molinette, Ematologia Universitaria
    • Contact: Federica Cavallo; Phone Number: 390116334264; Email: f.cavallo@unito.it
    • Principal Investigator: Federica Cavallo
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Istituto di Candiolo, IRCCS - Oncologia Medica ed Ematologia
      • Principal Investigator: Umberto Vitolo
      • Contact: Umberto Vitolo; Phone Number: 390116335934; Email: umberto.vitolo@ircc.it
• Spain
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra - Hematología y Hemoterapia
    • Contact: Miguel Canales Albendea; Phone Number: 34917277116; Email: macanales@unav.es
    • Principal Investigator: Migue Canales Albendea
  • Barcelona
    • Badalona, Barcelona, Spain, 8036
      • Hospital Clinic De Barcelona - Hematología
      • Principal Investigator: Pablo Mozas
      • Contact: Pablo Mozas; Phone Number: 34 93 227 22 71; Email: mozas@clinic.cat
    • L'Hospitalet de Llobregat, Barcelona, Spain, 8907
      • Institut Català d'Oncologia (ICO) - ICO L'Hospitalet - Hematologia
      • Principal Investigator: EVA DOMINGO DOMENECH
      • Contact: Eva Domingo Domenech; Phone Number: 34932607822; Email: edomingo@iconcologia.net
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra - Hematología
      • Contact: Miguel Canales Albendea; Phone Number: 34917277116; Email: macanales@unav.es
      • Principal Investigator: Miguel Canales Albendea
• United States
  • California
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center - Hematology/Oncology
      • Contact: Lauren Pinter Brown; Phone Number: 7144568200; Email: lpinterb@uci.edu
      • Principal Investigator: Lauren Pinter Brown
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
      • Principal Investigator: Youn Kim
      • Contact: Youn Kim; Phone Number: 650-723-7893; Email: younkim@stanford.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center - Research
      • Contact: Salvia Jain; Phone Number: 617-726-2000; Email: salvia.jain@mgh.harvard.edu
      • Principal Investigator: Salvia Jain
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Oncology Hospital - Public
      • Principal Investigator: Neha Mehta Shah
      • Contact: Neha Mehta Shah; Phone Number: 314.273-8566; Email: mehta-n@wustl.edu
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-2105
      • Hackensack University Medical Center - John Theurer Cancer C - Lymphoma Division
      • Principal Investigator: Tatyana Feldman
      • Contact: Tatyana Feldman; Phone Number: 551-996-5900; Email: tatyana.feldman@hmhn.org
  • New York
    • New York, New York, United States, 10021-6007
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Jasmine Zain
      • Contact: Jasmine Zain; Phone Number: 212-639-3045; Email: zainj1@mskcc.org
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas - MD Anderson Cancer Center
      • Principal Investigator: Ranjit Nair
      • Contact: Ranjit Nair; Phone Number: 171-379-2860; Email: rnair@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 and 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).
• 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. -

Exclusion Criteria:

• Recent autologous or allogeneic transplant within 120 days before treatment; active GVHD or ongoing immunosuppression after allogeneic transplant.
• Pregnant or breastfeeding females, or those intending pregnancy; males with partners intending pregnancy.
• History of HIV, HBV, or HCV infections generally excluded, except for controlled or resolved cases as defined.
• Uncontrolled infections requiring IV 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.
• 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.-

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part One (Dose Escalation); In Part 1, safety and tolerability of KK2223 in relapsed/refractory PTCL or CTCL patients will be assessed using a BOIN dose-escalation design.	Drug: KK2223; Intravenous infusion
Experimental: Part Two (Backfill); Part 2 will collect additional data, with dose levels and cohort size based on Part 1 results, administering doses approved for tolerability. Backfill cohorts at cleared doses may open, prioritizing Part 1 enrollment.	Drug: KK2223; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 (all 72 potentially treated subjects)	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).	Vital signs (mmHg in Systolic/Diastolic blood pressure)	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).	Pulse rate (beats/min)	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).	Respiratory Rate (breath/min)	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).	Temperature (°Celcius)	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).	ECG parameters (PR interval, QRS interval, QT interval, QTc interval)	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).	Number of participants with dose-limiting toxicities (DLTs) in Part 1 only (at most 27 participants) and assess maximum tolerated dose (MTD)	Through study completion, an average of 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the blood drug concentration		Through study completion, an average of 1.5 years
To evaluate the immunogenicity of KK2223.	Incidence of Anti drug antibodies (ADA) in blood	Through study completion, an average of 1.5 years
To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed).	% in Overall Response Rate (ORR)	Through study completion, an average of 1.5 years
To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed).	% in Compartment Response (if applicable)	Through study completion, an average of 1.5 years
To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed).	Time unit (week/month) in Duration of Response (DOR)	Through study completion, an average of 1.5 years
To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed).	Time unit (week/month) in Time To Next Treatment (TTNT) will be evaluated	Through study completion, an average of 1.5 years
To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed).	Time unit (week/month) in Time To Response (TTR)	Through study completion, an average of 1.5 years

Collaborators and Investigators

• Sponsor: Kyowa Kirin, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: August 12, 2025
• First Submitted That Met QC Criteria: September 17, 2025
• First Posted (Actual): September 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immune System Diseases; Neoplasms; Lymphoma; Mycosis fungoides; First in Human; Sezary Syndrome; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous +
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Hemic and Lymphatic Diseases; Neoplasms; Lymphoma; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Immune System Diseases; Mycosis Fungoides; Sezary Syndrome
• Other Study ID Numbers: 2223-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No