A Phase Ib Study to Evaluate the Safety and Tolerability of Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Patients With Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
Durvalumab and Tremelimumab in combination with first-line chemotherapy in the following indications: Ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC and gastric/GEJ cancer, PDAC, ESCC.
详细描述
7 cohorts of first-line chemotherapy regimens combined with durvalumab + tremelimumab.
This study will evaluate the safety and tolerability of durvalumab (MEDI4736) + tremelimumab in combination with first line chemotherapy regimens in patients with locally advanced or metastatic solid tumors: ovarian/peritoneal/fallopian tube cancer, squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC), small cell lung carcinoma (SCLC), and gastric/gastro-esophageal junction (GEJ) cancer, pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Patients with histologically or cytologically documented chemotherapy-naïve locally advanced unresectable or metastatic ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC, gastric cancer/GEJ, PDAC and ESCC.
- •ECOG performance status of 0 or 1
- •Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease
- •At least 1 lesion, not previously irradiated, that can be accurately measured at baseline
- •No prior exposure to immune-mediated therapy
- •Adequate organ and marrow function as defined below
排除标准
- •Receipt of any investigational anticancer therapy within 28 days or 5 halflives, whichever is longer, prior to the first dose of study treatment
- •Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment
- •Any unresolved Grade ≥2 toxicity from previous anticancer therapy
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from study drugs, or compromise the ability of the patient to give written informed consent
- •Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
- •Active tuberculosis
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
研究组 & 干预措施
Cohort 2
Small-cell lung cancer (SCLC)
干预措施: tremelimumab (Biological)
Cohort 1
ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN)
干预措施: paclitaxel + carboplatin (Drug)
Cohort 1
ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN)
干预措施: durvalumab (Biological)
Cohort 1
ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN)
干预措施: tremelimumab (Biological)
Cohort 2
Small-cell lung cancer (SCLC)
干预措施: carboplatin + etoposide (Drug)
Cohort 2
Small-cell lung cancer (SCLC)
干预措施: durvalumab (Biological)
Cohort 3
Triple-negative breast cancer (TNBC)
干预措施: gemcitabine + carboplatin (Drug)
Cohort 3
Triple-negative breast cancer (TNBC)
干预措施: durvalumab (Biological)
Cohort 3
Triple-negative breast cancer (TNBC)
干预措施: tremelimumab (Biological)
Cohort 4
Triple-negative breast cancer (TNBC)
干预措施: nab-paclitaxel (paclitaxel-albumin) + carboplatin (Drug)
Cohort 4
Triple-negative breast cancer (TNBC)
干预措施: durvalumab (Biological)
Cohort 4
Triple-negative breast cancer (TNBC)
干预措施: tremelimumab (Biological)
Cohort 5
Gastric/gastro-esophageal junction (GEJ)
干预措施: oxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid) (Drug)
Cohort 5
Gastric/gastro-esophageal junction (GEJ)
干预措施: durvalumab (Biological)
Cohort 5
Gastric/gastro-esophageal junction (GEJ)
干预措施: tremelimumab (Biological)
Cohort 6
Pancreatic ductal adenocarcinoma (PDAC)
干预措施: durvalumab (Biological)
Cohort 6
Pancreatic ductal adenocarcinoma (PDAC)
干预措施: tremelimumab (Biological)
Cohort 6
Pancreatic ductal adenocarcinoma (PDAC)
干预措施: nab-paclitaxel (paclitaxel-albumin) + gemcitabine (Drug)
Cohort 7
Esophageal squamous cell carcinoma (ESCC)
干预措施: durvalumab (Biological)
Cohort 7
Esophageal squamous cell carcinoma (ESCC)
干预措施: tremelimumab (Biological)
Cohort 7
Esophageal squamous cell carcinoma (ESCC)
干预措施: cisplatin + 5-fluorouracil (5FU) (Drug)
结局指标
主要结局
Incidence of Adverse Events
时间窗: Throughout the study, approximately three years
To assess incidence of Adverse Events for the safety and tolerability profile of first-line chemotherapy in combination with durvalumab and tremelimumab
Laboratory findings (including: clinical chemistry, hematology, and urinalysis)
时间窗: Throughout the study, approximately three years
To assess the safety and tolerability profile of first-line chemotherapy in combination with durvalumab + tremelimumab
Tumor assessment based on RECIST 1.1 (for cohort 6 only)
时间窗: Throughout the study, approximately three years (for cohort 6 only)
To estimate the objective response rate (ORR) of durvalumab + tremelimumab + chemotherapy (for cohort 6 only)
次要结局
未报告次要终点