A Phase I/II Open-label, Multi-center Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Part B (Dose Expansion): Number of Participants With AEs
研究概览
简要总结
The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of sabestomig (AZD7789) in patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL).
详细描述
This is a Phase I/II, open-label multi-center study will have sabestomig administered via intravenous infusion on Cycle 1 Day 1 to adult/young adult patients with relapsed/refractory classical Hodgkin Lymphoma (r/r cHL). This study will have 2 parts: Phase 1 (Part A) Dose Escalation and Phase 2 (Part B) Dose Expansion.
Patients will be treated with study intervention for a maximum of 35 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue treatment occur.
The trial was intended to be Phase I/II trial (but the trial never moved forward to Phase 2). Hence, the study Phase was updated to Phase I.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 101 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 16 years of age at the time of obtaining informed consent
- •Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
- •At least one positron emission tomography (PET)-avid measurable lesion according to Modified Lugano Criteria after the last line of therapy.
- •Confirmed histological diagnosis of active relapse/refractory cHL
- •Failed at least 2 prior lines of systemic therapy.
- •No previous treatment with anti-TIM-
- •Adequate organ and bone marrow function
- •Non-pregnant women and willingness of female patients to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
- •Minimum body weight ≥ 40 kg for all participants.
排除标准
- •Unresolved toxicities of ≥ Grade 2 from prior therapy
- •Any prior ≥ Grade 3 imAE while receiving prior checkpoint inhibitor immunotherapy
- •Patients with central nervous system (CNS) involvement or leptomeningeal disease.
- •History of allogeneic stem cell transplant or organ transplantation.
- •Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
- •Active infection including Tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
- •History of arrhythmia which is requires treatment, symptomatic or uncontrol led atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
- •Uncontrolled intercurrent illness.
- •Active or prior documented pathologically confirmed autoimmune or inflammatory disorders.
- •Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD
- •Other invasive malignancy within 2 years prior to screening
- •Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
- •Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
- •Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
研究组 & 干预措施
Cohort A: Dose Escalation
Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig to determine the recommended phase 2 dose (RP2D).
干预措施: Sabestomig (AZD7789) (Drug)
Cohort B1: Dose Expansion
Patients with anti-PD-1/PD-L1 exposed r/r cHL will receive sabestomig once the RP2D has been determined.
干预措施: Sabestomig (AZD7789) (Drug)
Cohort B2: Dose Expansion
Patients with anti-PD-1/PD-L1 naïve r/r cHL will receive sabestomig once the RP2D has been determined.
干预措施: Sabestomig (AZD7789) (Drug)
结局指标
主要结局
Part B (Dose Expansion): Number of Participants With AEs
时间窗: Up to approximately 2 years 90 days
The safety and tolerability of sabestomig in participants with r/r cHL was planned to be assessed.
Part A (Dose Escalation): Number of Participants With Adverse Events (AEs)
时间窗: From start of treatment [Cycle 1 Day 1 (C1D1) (each cycle was 28 days)] up to 90 days post last dose (approximately 2 years 5 months)
The safety and tolerability of sabestomig in participants with r/r cHL were assessed.
Part A (Dose Escalation): Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: From first dose (C1D1) until 28 days for each participant [within 28 days DLT period]
DLT was defined as any ≥Grade 3 AE as per NCI CTCAE version 5 unless unequivocally due to underlying malignancy or an extraneous cause. The following conditions were considered as DLTs: * Any death not clearly due to the underlying disease or extraneous causes * Grade 4 imAE or anemia * Any ≥Grade 3 non-infectious pneumonitis or colitis of any duration * Specific liver transaminase elevation as per protocol * Any Grade 3 imAE, including rash, pruritus, or diarrhea, that does not downgrade to Grade 2 or less within 7 days * Grade 3 nausea, vomiting, or diarrhea that does not resolve to Grade 2 or less within 3 days of getting maximal supportive care * ≥Grade 3 neutropenia, without fever or systemic infection, that does not improve by at least one grade within 7 days * Grade 4 thrombocytopenia for more than 7 days or ≥Grade 3 thrombocytopenia along with Grade ≥2 bleeding * Grade 4 Cytokine Release Syndrome (CRS) of any duration or Grade 3 CRS not improving to Grade ≤2 within 72 hours
Part B (Dose Expansion): Cohort B1: Objective Response Rate (ORR)
时间窗: Up to approximately 2 years 90 days
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. ORR was defined as the percentage of participants with an objective response \[Best Overall Response of a complete response (CR) or partial response (PR)\] as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).
Part B (Dose Expansion): Cohort B2: Complete Response Rate (CRR)
时间窗: Up to approximately 2 years 90 days
The anti-tumor activity of sabestomig in participants with r/r cHL was planned to be assessed. The CRR was defined as the percentage of participants with a CR as per modified Lugano criteria (Lugano 2014), with the denominator defined as the number of participants in the response-evaluable analysis set. Disease response was planned to be assessed according to Blinded Independent Central Review using modified Lugano criteria (Lugano 2014).
次要结局
- Part B (Dose Expansion): Duration of Response (DoR)(Up to approximately 2 years 90 days)
- Part A (Dose Escalation): Complete Response Rate (CRR)(From start of treatment [C1D1 (each cycle was 28 days)] until first documented disease progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months))
- Part A (Dose Escalation): Objective Response Rate (ORR)(From start of treatment [C1D1 (each cycle was 28 days)] until progression, or last evaluable assessment in the absence of progression (up to 2 years 5 months))
- Part A (Dose Escalation): Duration of Response (DoR)(From first documented response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months))
- Part A (Dose Escalation): Duration of Complete Response (DoCR)(From first documented complete response until date of first documented disease progression or death from any cause, or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months))
- Part A (Dose Escalation): Progression-free Survival (PFS)(From start of treatment [C1D1 (each cycle was 28 days)] until date of first documented disease progression or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months))
- Part A (Dose Escalation): Overall Survival (OS)(From start of treatment [C1D1 (each cycle was 28 days)] until date of death due to any cause or data cut-off or end of study (whichever came first, assessed up to 2 years 5 months))
- Part A (Dose Escalation): Number of Participants With Positive Anti-drug Antibodies (ADA) Against Sabestomig in Serum(On C1D1, C2D1, and until end of study [up to 2 years 5 months (each cycle was 28 days)])
- Part A (Dose Escalation): Maximum Observed Concentration (Cmax)(From C1D1 [before start of infusion (SOI) and at end of infusion (EOI)] to end of study [up to 2 years 5 months (each cycle was 28 days)])
- Part A (Dose Escalation): Area Under the Concentration-time Curve (AUC)(From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)])
- Part A (Dose Escalation): Clearance (CL)(From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)])
- Part A (Dose Escalation): Terminal Elimination Half-life (t½λz)(From C1D1 (before SOI and at EOI) to end of study [up to 2 years 5 months (each cycle was 28 days)])
- Part B (Dose Expansion): Duration of Complete Response (DoCR)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Progression-free Survival (PFS)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Overall Survival (OS)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Number of Participants With Positive ADA Against Sabestomig in Serum(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Maximum Observed Concentration (Cmax)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Area Under the Concentration-time Curve (AUC)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Terminal Elimination Half-life (t½λz)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Pediatric Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (Peds-PRO-CTCAE)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): Patient Global Impression of Treatment Tolerability (PGI-TT)(Up to approximately 2 years 90 days)
- Part B (Dose Expansion): European Organization for Research and Treatment of Cancer (EORTC) Item List (IL)XX QL2 [2-item Global Health-related Quality of Life (HRQoL)](Up to approximately 2 years 90 days)