A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas

Inclusion criteria

(All Subjects):

• ≥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).

Exclusion criteria

Disease-specific Exclusion Criteria; LGLL and ANKL:

• A reactive LGL lymphocytosis to a viral infection or LGL associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

The following exclusion criteria apply to all subjects:

• Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.
• Active or suspected malignant central nervous system involvement.
• Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).
• Active known second malignancy.
• Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).
• Hepatitis B infection (hepatitis B virus surface antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Subjects with HCV with undetectable virus after treatment are eligible.
• History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.
• Use of systemic corticosteroids at prohibited dose levels within 15 days prior to C1D1 (except for prophylaxis for radiodiagnostic contrast reactions and study-defined premedication) or use of other non-biological immunosuppressive drugs within 15 days or 5 half-lives (whichever is less) prior to C1D1.
• Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).
• Any other medical or psychiatric condition, or laboratory abnormality that would increase the risk associated with study participation, in the opinion of the Investigator or Medical Monitor.
• Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, peripheral neuropathy, or hematologic parameters meeting inclusion criteria).
• Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days
• Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.
• Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).