Phase 1b, Open-label, Dose Escalation and Cohort Expansions Trial of Naptumomab Estafenatox (NAP, ABR-217620) in Combination with Durvalumab (MEDI4736) in Subjects with Selected Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- Other (Terminated)
- 发起方
- 入组人数
- 54
- 试验地点
- 9
- 主要终点
- 1. ORR by (iRECIST) of the combination of NAP with durvalumab in subjects with advanced/metastatic:
研究概览
简要总结
To assess the Efficacy, safety and tolerability of Naptumomab Estafenatox/ Durvalumab in Esophageal cancer patients.
Rational for the Combination of NAP and Durvalumab for the Treatment of Esophageal Cancer
While a few early-phase trials have taken place in India for cancer research, this study can provide a solid foundation for future research. Particularly in the case of current trial, where safety profile for NAP in combination with durvalumab, has already been well established at the recommended phase 2 dose (RP2D), and this is a cohort expansion that will be conducted globally in the India US and Israel.
NAP recognizes the 5T4 antigen and induces T-cell-mediated killing of tumor cells. Thetherapeutic effect of NAP is associated with activation of SAg-binding T cells. TheSAg-binding T lymphocytes expand, differentiate into effector cells, and infiltrate the****tumor.
This effect of NAP makes it an ideal drug for combination with checkpoint inhibitorssince recognition is not only a requirement for the initial response of checkpointinhibitors but loss of recognition is also a major cause of acquired resistance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Group 1 no prior CPI: Subjects with only ESCC who may have received up to 1 prior chemotherapy as a line for metastatic disease or up to 2 prior chemotherapies if they also received neoadjuvant/adjuvant systemic therapy, but no prior CPI.
- •If subjects received prior chemotherapy for metastatic disease, they should have documented radiographic or clinical progression.
- •Group 2 -prior CPI: a.
- •Subjects with either ESCC or AC or GEJ (Siewert type 1) who must not have had more than 2 prior lines of therapy.
- •Patients will be allowed to have up to 2 prior regimens for metastatic disease, or up to 3 prior therapies if they also received neoadjuvant/adjuvant systemic therapy.
- •Subjects are eligible provided that they have received CPI therapy for at least 9 weeks, provided that they have documented progression of their disease on such therapy, and provided that prior CPI was not discontinued for toxicity.
- •No more than 1 prior checkpoint inhibitor treatment is allowed (prior combination of anti-PD-(L) 1 and anti-CTLA-4 is acceptable).
- •Subjects with adenocarcinoma that are HER-2/neu negative.
排除标准
- •Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF), myocardial infarction, or acute coronary syndrome within 6 months prior to study enrollment, ongoing angina pectoris, severe peripheral vascular disease, cerebrovascular accident (CVA) within 6 months of study entry, or any other concomitant medical disorder that might interfere with the subject’s participation in the study or interpretation of the study data.
- •Subjects who have undergone major surgery or trauma within 4 weeks of study entry.
- •Recent history of live attenuated vaccine within 28 days prior to obinutuzumab.
- •NOTE: Patients, once enrolled, should not receive live vaccine whilst receiving study drug and up to 30 days after the last dose of study drug.
- •Known current drug or alcohol abuse.
- •Known active or latent tuberculosis (TB) infection (purified protein derivative [PPD] test is not required) as indicated by any of the following: PPD recently converted to positive; chest x-ray with evidence of infections infiltrate.
结局指标
主要结局
1. ORR by (iRECIST) of the combination of NAP with durvalumab in subjects with advanced/metastatic:
时间窗: over the period of 24 months and 28 cycles
a) squamous cell carcinoma of the esophagus without exposure to prior anti-PD-1/PD-L1 therapy, and b) squamous cell carcinoma or adenocarcinoma of the esophagus or the esophago-gastric junction, who have received prior anti-PD-1/PDL1
时间窗: over the period of 24 months and 28 cycles
therapy.
时间窗: over the period of 24 months and 28 cycles
次要结局
- 1. To assess clinical activity in terms of overall survival (OS),(progression-free survival (PFS), duration of response (DOR) and)
研究者
Radhika Inapakolla
CliNovi Research Pvt. Ltd.