2022-502759-70-01招募中2 期
A Phase I/IIa Multi-center, Open-label Master Protocol to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of AZD8205 in Participants with Advanced or Metastatic Solid Malignancies.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 97
- 试验地点
- 21
- 主要终点
- Incidence of AEs/SAEs
研究概览
简要总结
To assess the safety and tolerability and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of AZD8205 as monotherapy and in combination with anticancer agents.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Sub-study 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •For Sub-Study 2 Part A: Minimum body weight ≥ 30 kg.
- •For Sub-Study 4 Part A: • Minimum body weight ≥ 30 kg. • Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, endometrial cancer or squamous non-small cell lung cancer.
- •For Sub-Study 2 Part A: Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer.
- •Relapsed/metastatic solid tumors treated with prior adequate standard of care therapy for tumor type and stage of disease or where in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy.
- •Measurable disease per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
- •Life expectancy ≥ 12 weeks
- •Adequate organ and marrow function as defined in the protocol
- •For Sub-Study 1 Part A: Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer
- •For Sub-Study 1 Part B: Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort: a) Cohort B1 (Biliary Tract Cancer) b) Cohort B2 (Ovarian Cancer) c) Cohort B3 (Breast Cancer) d) Cohort B4 (Endometrial Cancer) e) Cohort B5 (Squamous Non-Small Cell Lung Cancer)
排除标准
- •Treatment with any of the following:
- •Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment
- •Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study treatment
- •Any other anticancer treatment within the following time periods prior to the first dose of study intervention: a. Cytotoxic treatment: 21 days b. Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter) c. Biological products including immuno-oncology agents: 28 days
- •Additional Exclusion Criteria for Part A Sub study 2: Thromboembolic event within 3 months before the first dose of study intervention.
- •For Sub-Study 4 Part A: • Patients have received prior therapy with AZD9574 or more than 1 prior line of any other PARPi-based regimen (either as a treatment or as maintenance). Prior treatment with rilvegostomig. • Medical conditions: history or persisting severe cytopenia, history of uncontrolled seizures, known predisposition to bleeding, refractory nausea, vomiting, chronic gastrointestinal diseases. History of organ transplant.
- •Additional Exclusion Criteria for Part A Sub study 2: Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- •Additional Exclusion Criteria for Part A Sub study 2: Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
- •Spinal cord compression or a history of leptomeningeal carcinomatosis.
- •Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study.
- •Active infection including tuberculosis, SARS-CoV-2 and HBV, HCV or HIV
- •History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
- •Participants with any of the following cardiac criteria:
- •History of arrhythmia which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia.
- •Uncontrolled hypertension.
- •Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.
- •History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
- •Symptomatic heart failure (NYHA class ≥ 2).
- •Prior or current cardiomyopathy.
- •Severe valvular heart disease.
- •Mean resting QTcF > 470 msec.
- •Risk factors for QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
结局指标
主要结局
Incidence of AEs/SAEs
Incidence of AEs/SAEs
Incidence of DLTs
Incidence of DLTs
Changes from baseline in laboratory findings, ECGs and vital signs
Changes from baseline in laboratory findings, ECGs and vital signs
Changes in physical examination (including ECOG)
Changes in physical examination (including ECOG)
次要结局
- Radiological response evaluated according to RECIST v1.1 - objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS).
- Serum concentrations of AZD8205, anti-B7-H4 antibody (INT016) and unconjugated payload (AZ14170132).
- Pharmacodynamics (PK) parameters of AZD8205, INT016 and AZ14170132, including but not limited to area under the concentration-time curve (AUC), maximum observed concentration (Cmax), time to reach maximum concentration (tmax), clearance and half-life, as data allow.
- The number and percentage of participants who develop anti-drug antibody (ADAs).
- Additional Sub Study 1 Secondary end points: Changes in tumor cell γH2AX protein expression on treatment.
- Additional Sub Study 2 Secondary end points: Changes in tumor cell γH2AX protein expression on treatment.
- Additional Sub Study 2 Secondary end points: Serum concentrations and PK parameters (where applicable) of rilvegostomig; Incidence of ADAs against rilvegostomig in serum
- Additional Sub study 4 secondary endopoints: Plasma concentration and PK parameters of AZD9574 Serum concentrations and PK parameter (where applicable) of rilvegostomig The number and percentage of participants who develop ADAs.
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (21)
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