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
概览
- 阶段
- 1 期
- 干预措施
- DR-01
- 疾病 / 适应症
- 未指定
- 发起方
- Dren Bio
- 入组人数
- 200
- 试验地点
- 40
- 主要终点
- Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0.
- 状态
- 招募中
- 最后更新
- 15天前
概览
简要总结
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
研究者
入排标准
入选标准
- •(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-
- •Male subjects must agree to use acceptable effective method(s) of contraception.
- •Subjects with LGLL must also meet inclusion criteria 6 and
- •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):
排除标准
- •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.
研究组 & 干预措施
Part A Dose Escalation 6 mg/kg of DR-01
Subjects in this arm will initially receive 6 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
干预措施: DR-01
Part A Dose De-escalation 0.3 to <1 mg/kg of DR-01
This cohort would only be triggered should a DLT occur at Dose Level 1 or if recommended by the Safety Review Committee. Subjects in this arm would initially receive 0.3 to \<1 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 3 mg/kg) thereafter for up to 25 cycles total.
干预措施: DR-01
Part A Dose Escalation 1 mg/kg of DR-01
Subjects in this arm will initially receive 1 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 6 mg/kg) thereafter for up to 25 cycles total.
干预措施: DR-01
Part A Dose Escalation 3 mg/kg of DR-01
Subjects in this arm will initially receive 3 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
干预措施: DR-01
Part A Dose Escalation 10 mg/kg of DR-01
Subjects in this arm will initially receive 10 mg/kg at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 cycles total.
干预措施: DR-01
Part B Dose Expansion (Cohort B1) Optimized Dose/Regimen of DR-01
Subjects in this arm will receive the pharmacologically optimized dose/regimen for LGL leukemia subjects determined in Part A. Depending on the selected dose/regimen, subjects will receive target dose at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing thereafter for up to 25 doses total.
干预措施: DR-01
Part B Dose Expansion (Cohort B2) Optimized Dose/Regimen of DR-01
Subjects in this arm will receive the pharmacologically optimized dose/regimen for cytotoxic lymphoma subjects determined in Part A. Depending on the selected dose/regimen, subjects will receive target dose at either the Primary regimen (bi-weekly dosing for fist month), Secondary regimen (doses at Days 1, 8, 15, 29 during first month), or Tertiary regimen (dosing days 1-5, 15, 29 during first month), followed by monthly dosing thereafter for up to 25 doses total.
干预措施: DR-01
结局指标
主要结局
Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: Up to 24 months