Aggressive NK Cell Leukemia, Cutaneous PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker), Cytotoxic PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker), Enteropathy-Associated T-Cell Lymphoma, Extranodal NK/T Cell Lymphoma, Nasal Type, Hepatosplenic T-cell Lymphoma, Hydroa Vacciniforme-Like Lymphoproliferative Disorder, LGLL - Large Granular Lymphocytic Leukemia, Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma, Primary Cutaneous CD8+ Aggressive Epidermotropic T-Cell Lymphoma, Primary Cutaneous Gamma-Delta T-Cell Lymphoma, Subcutaneous Panniculitis-Like T-Cell Lymphoma, Systemic EBV1 T-cell Lymphoma, if CD8 Positive
Conditions
Keywords
LGLL, Cytotoxic, Lymphoma, ANKL, EATL, MEITL, ENKL, HSTCL, Leukemia, SPTCL, ENKTL, CTCL, PTCL-NOS, TCL
Brief summary
This is a multicenter, first-in-human, Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DR-01 in adult patients with large granular lymphocytic leukemia or cytotoxic lymphomas
Interventions
DRUGDR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.
Sponsors
Dren Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(All Subjects): 1. ≥18 years of age. 2. Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document. 3. Sufficient key organ performance and coagulation. 4. Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least one ovary, and is \<1 year postmenopausal) must agree to use a highly effective method of contraception from enrollment through at least 12 months after last dose of DR-01. 5. Male subjects must agree to use acceptable effective method(s) of contraception. Subjects with LGLL must also meet inclusion criteria 6 and 7. 6. Must have discontinued at least one prior line of systemic therapy. 7. Additional immunophenotypic and symptomatic criteria must be met. Disease-specific Inclusion Criteria (Cytotoxic Lymphomas): Subjects with cytotoxic lymphomas must also meet inclusion criteria 8,9, and 10. 8. Subjects must have failed at least one prior systemic regimens. 9. Availability of post-progression tissue sample or willingness to consent to a baseline biopsy. 10. Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification \[Swerdlow 2016\]). 11. For Part A only, evaluable disease is acceptable. 12. For Part B2 only, evaluable by the following response criteria as documented during Screening: 1. For cytotoxic PTCL-NOS, ENKTL, MEITL, EATL, SPTCL - Subjects must have radiographically measurable disease by computed tomography (CT) or CT/positron emission tomography (PET) scan defined as at least one node measuring \>1.5 cm or measurable extranodal lesion of at least 1.0 cm in longest diameter to be evaluated by Lugano criteria (Cheson 2014). 2. For PCGDTCL, ET-CTCL, HVLPD, cytotoxic CuPTCL-NOS - Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or have leukemic involvement that can be evaluated using modified TPLL response criteria (Staber 2019). 3. For HSTCL, ANKL, SysEBV TCL - Subjects with hepatosplenic disease without measurable disease by Lugano criteria (Cheson 2014) or leukemic involvement in BM or peripheral blood that is evaluable for response using a modified TPLL response criteria (Staber 2019).
Exclusion criteria
Disease-specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0. | Up to 25 months |
| Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria. | During First 28 days (Cycle 1) |
| Part A: To determine potential pharmacologically optimized dose/regimen for DR-01 in LGL leukemia and cytotoxic lymphoma populations as determined using an integrated assessment of efficacy, safety, PK/PD, and exposure-response relationships. | Up to 6 months |
| Part B: Overall Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) based on disease-specific response criteria. | Up to 24 months |
Countries
Australia, France, Germany, Hong Kong, Italy, South Korea, Spain, Taiwan, United States
Contacts
CONTACTDren Central Contact
STUDY_DIRECTORWan-Jen Hong, MD
Dren Bio
Outcome results
None listed