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NCT05475925PHASE1, PHASE2Recruiting

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

Dren Bio

Start Date

7/13/2022

Completion Date

12/1/2026

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

Eligibility Criteria

Age Range: 18 years to No maximum

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 Exclusion Criteria; LGLL and ANKL: 1. 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: 2. Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals. 3. Active or suspected malignant central nervous system involvement. 4. Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation). 5. Active known second malignancy. 6. Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2). 7. 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. 8. History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II. 9. 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. 10. Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy). 11. 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. 12. 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). 13. Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days 14. Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT. 15. Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).

Interventions

DRUG

DR-01

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Conditions

LGLL - Large Granular Lymphocytic LeukemiaPrimary Cutaneous Gamma-Delta T-Cell LymphomaPrimary Cutaneous CD8+ Aggressive Epidermotropic T-Cell LymphomaHepatosplenic T-cell LymphomaSubcutaneous Panniculitis-Like T-Cell LymphomaAggressive NK Cell LeukemiaSystemic EBV1 T-cell Lymphoma, if CD8 PositiveHydroa Vacciniforme-Like Lymphoproliferative DisorderExtranodal NK/T Cell Lymphoma, Nasal TypeEnteropathy-Associated T-Cell LymphomaMonomorphic Epitheliotropic Intestinal T-Cell LymphomaCytotoxic PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker)Cutaneous PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker)

Locations

Dren Investigational Site

Birmingham, Alabama 35233

United States

Dren Investigational Site

Duarte, California 91010

United States

Dren Investigational Site

Irvine, California 92612

United States

Dren Investigational Site

Redwood City, California 94063

United States

Dren Investigational Site

New Haven, Connecticut 06519

United States

Dren Investigational Site

Tampa, Florida 33612

United States

Dren Investigational Site

Boston, Massachusetts 02114

United States

Dren Investigational Site 1

New York, New York 10021

United States

Dren Investigational Site 2

New York, New York 10032

United States

Dren Investigational Site

Columbus, Ohio 43210

United States

Dren Investigational Site 2

Pittsburgh, Pennsylvania 15213

United States

Dren Investigational Site

Houston, Texas 77030

United States

Dren Investigational Site

Charlottesville, Virginia 22903

United States

Dren Investigational Site

Fairfax, Virginia 22031

United States

Dren Investigational Site

Seattle, Washington 98109

United States

Dren Investigational Site

Clayton, Victoria 3168

Australia

Dren Investigational Site

Richmond, Victoria 3121

Australia

Dren Investigational Site

Nedlands, Washington 6009

Australia

Dren Investigational Site

Pierre-Bénite, 69310

France

Dren Investigational Site

Rennes, 35000

France

Dren Investigational Site

Toulouse, 31059

France

Dren Investigational Site

Berlin, 10117

Germany

Dren Investigational Site

Cologne, 50937

Germany

Dren Investigational Site

Leipzig, 04103

Germany

Dren Investigational Site 1

Hong Kong, Hong Kong

Hong Kong

Dren Investigational Site 2

Hong Kong,

Hong Kong

Dren Investigational Site

Bologna, 40126

Italy

Dren Investigational Site 1

Busan,

South Korea

Dren Investigational Site 2

Busan,

South Korea

Dren Investigational Site

Goyang-si,

South Korea

Dren Investigational Site 1

Seoul,

South Korea

Dren Investigational Site 2

Seoul,

South Korea

Dren Investigational Site 3

Seoul,

South Korea

Dren Investigational Site

Barcelona, 08035

Spain

Dren Investigational Site

Salamanca, 37007

Spain

Dren Investigational Site

Tainan,

Taiwan

Dren Investigational Site

Taipei,

Taiwan