A Multicenter, Open-Label, First-In-Human, Multiple Expansion Cohort, Phase 1/2 Study to Evaluate the Safety and Efficacy of DR-01 in Adult Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas
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
• ≥18 years of age.
• Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
• Sufficient key organ performance and coagulation.
• 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.
• Male subjects must agree to use acceptable effective method(s) of contraception.
• Subjects with LGLL must also meet inclusion criteria 6 and 7.
• Must have discontinued at least one prior line of systemic therapy.
• 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.
• Subjects must have failed at least one prior systemic regimens.
• Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.
⁃ Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification \[Swerdlow 2016\]).
⁃ For Part A only, evaluable disease is acceptable.
⁃ For Part B2 only, evaluable by the following response criteria as documented during Screening:
∙ 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).
‣ 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).
‣ 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).