A First-in-Human Study of KK2223 in Participants With Relapsed or Refractory T Cell Non-Hodgkin Lymphoma
Not Applicable
Not yet recruiting
- Conditions
- T-cell NHL (PTCL or CTCL)
- Interventions
- Drug: KK2223
- Registration Number
- NCT07192471
- Lead Sponsor
- Kyowa Kirin, Inc.
- Brief Summary
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).
- 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)
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 72
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part One (Dose Escalation) KK2223 In Part 1, safety and tolerability of KK2223 in relapsed/refractory PTCL or CTCL patients will be assessed using a BOIN dose-escalation design. Part Two (Backfill) KK2223 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.
- Primary Outcome Measures
Name Time Method 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). Through study completion, an average of 1.5 years Number of participants with dose-limiting toxicities (DLTs) in Part 1 only (at most 27 participants) and assess maximum tolerated dose (MTD)
- Secondary Outcome Measures
Name Time Method To evaluate the preliminary anti-tumor activity of KK2223 (Investigator assessed). Through study completion, an average of 1.5 years Time unit (week/month) in Time To Response (TTR)
To evaluate the blood drug concentration Through study completion, an average of 1.5 years To evaluate the immunogenicity of KK2223. Through study completion, an average of 1.5 years Incidence of Anti drug antibodies (ADA) in blood