Pembrolizumab 在未知原发性癌症中的试验 (CUPem)

实验性的：派姆单抗

所有试验治疗都将在门诊进行。 Pembrolizumab 200 mg 将作为每 3 周一次的 30 分钟静脉输注给药。 站点应尽一切努力将输液时间设定为尽可能接近 30 分钟。 然而，考虑到不同地点输液泵的可变性，-5 分钟和 +10 分钟的窗口是允许的（即，输液时间为 30 分钟：-5 分钟/+10 分钟）。

药品：派姆单抗

根据临床前体外数据，派姆单抗对 PD-1 具有高亲和力和强效受体阻断活性。 Pembrolizumab 具有可接受的临床前和临床安全性，并且正在作为晚期恶性肿瘤的 IV 免疫疗法进行临床开发。

PD-1 通路代表了一个主要的免疫控制开关，它可能被肿瘤细胞参与以克服主动 T 细胞免疫监视。 Pembrolizumab 是一种有效且高度选择性的免疫球蛋白 (IgG4)/kappa 同种型人源化 mAb，旨在直接阻断 PD-1 与其配体 PD-L1 和 PD-L2 之间的相互作用。 这种阻断增强了靶淋巴细胞的功能活性，以促进肿瘤消退和最终的免疫排斥。

其他名称：

• 可瑞达

Overall Response Rate (ORR) by RECIST Criteria v1.1 in the Second-line & First-line Setting.

The Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. classifies response based on the assessment of target and non-target lesions on CT scans as:

Complete Response (CR): requires all of:

• disappearance of all target and non-target lesions
• pathological lymph nodes must have reduced to <10 mm in short axis
• no new lesions

Partial Response (PR): requires all of:

• at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters
• non-progressive disease of non-target lesions
• no new lesions

Progressive Disease (PD): either one of:

• any new lesions
• at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient

Stable Disease (SD): not meeting criteria for PD or PR.

Incidence Proportion of Adverse Events up to 8 Weeks After the Last Dose of Pembrolizumab in the Second Line Setting

The number of patients with any recorded adverse events (AE) defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the trial.

The incidence proportion or cumulative incidence is the percentage (%) of patients developing new AEs out of the total number at risk followed during that time frame.

Incidence of Adverse Events up to 8 Weeks After the Last Dose of Pembrolizumab in Performance Status 2 (PS2) Patients in Any Setting

The number of patients whose Performance Status was equal to two at baseline, with any recorded adverse events (AE) defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the trial.

The incidence proportion or cumulative incidence is the percentage (%) of patients developing new AEs out of the total number at risk followed during that time frame.

Identification of Potential Genomic Biomarkers Predictive of Immune Response to Pembrolizumab

This would be a retrospective analysis of blood samples collected for future research purposes only. Research bloods will be used to examine DNA and measure various blood biomarkers. These biomarkers may predict possible response to study treatment. As these samples are being taken before, during and after treatment, they will help us understand how the study treatments work. This will also enable us to learn whether or not the treatments have the desired effect, and to understand if these effects may be beneficial for the treatment of cancer of unknown primary (CUP). This information may also be used to develop and test other new treatments in the future. The panel of potential biomarkers against which the blood plasma will be tested has not been established yet. Information gained from this research component is not directly beneficial to patients taking part in this clinical trial.