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

Официальное название

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

Обзор

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

Вмешательства

• Препарат DR-01
  DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Первичные конечные точки

• Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: Up to 24 months]

Критерии участия

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).

Критерии исключения

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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• Dren Investigational Site — Birmingham
• Dren Investigational Site — Duarte
• Dren Investigational Site — Irvine
• Dren Investigational Site — Redwood City
• Dren Investigational Site — New Haven
• Dren Investigational Site — Tampa
• Dren Investigational Site — Boston
• Dren Investigational Site 1 — New York
• … и ещё 7 центров

South Korea · 6 центров

• Dren Investigational Site 1 — Busan
• Dren Investigational Site 2 — Busan
• Dren Investigational Site — Goyang-si
• Dren Investigational Site 1 — Seoul
• Dren Investigational Site 2 — Seoul
• Dren Investigational Site 3 — Seoul

Австралия · 3 центра

• Dren Investigational Site — Clayton
• Dren Investigational Site — Richmond
• Dren Investigational Site — Nedlands

Франция · 3 центра

• Dren Investigational Site — Pierre-Bénite
• Dren Investigational Site — Rennes
• Dren Investigational Site — Toulouse

Германия · 3 центра

• Dren Investigational Site — Berlin
• Dren Investigational Site — Cologne
• Dren Investigational Site — Leipzig

Гонконг · 2 центра

• Dren Investigational Site 1 — Гонконг
• Dren Investigational Site 2 — Гонконг

Испания · 2 центра

• Dren Investigational Site — Barcelona
• Dren Investigational Site — Salamanca

Тайвань · 2 центра

• Dren Investigational Site — Tainan
• Dren Investigational Site — Taipei

Италия · 1 центр

• Dren Investigational Site — Bologna

Идентификаторы

NCT: NCT05475925 · DR-01-ONC-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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