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 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 two 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:
‣ Subjects must have radiographically measurable disease to be assessed by Lugano criteria. Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or leukemic involvement that can be evaluated using a modified TPLL response criteria (Staber 2019).
‣ Subjects with hepatosplenic disease or other variants that do not have measurable disease by Lugano criteria (Cheson 2014) may be eligible upon discussion with the Medical Monitor if they have identifiable leukemic involvement in BM or peripheral blood (meeting the CD8+ cytotoxic phenotype definition) that can be evaluated for response using a modified TPLL response criteria (Staber 2019), or skin involvement that can be evaluated using Olsen criteria (Olsen 2021).