Gogas Helen, Ravimohan Shruthi, Datta Antara, Chhibber Aparna, Couselo Eva Muñoz, Diab Adi, Pereira Caio, Quéreux Gaëlle, Sandhu Shahneen, Curti Brendan, Khushalani Nikhil I, Taylor Matthew H, Daniels Gregory A, Spreafico Anna, Meniawy Tarek, Van Den Eertwegh Alfons J M, Sun Yongliang, Arriaga Yull, Zhou Ming, Long Georgina V, Lebbé Céleste
National and Kapodistrian University of Athens, Athens, Greece.
Bristol Myers Squibb, Princeton, NJ, USA.
NPJ Precis Oncol. 2024 Jul 19;8(1):150. doi: 10.1038/s41698-024-00641-7.
In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001.
在PIVOT IO 001（NCT03635983）研究中，研究性白细胞介素-2激动剂贝姆培加德白素（BEMPEG）与纳武单抗（NIVO）联合使用，对于不可切除/转移性黑色素瘤患者而言，相较于NIVO单药治疗并无额外的临床获益。对选定生物标志物的预定义基线及治疗期间变化进行分析，以探究临床观察结果背后的潜在机制。在每个治疗组中，与较低水平相比，较高的基线肿瘤突变负荷或免疫浸润/炎症与更好的疗效相关。治疗期间外周生物标志物变化显示，BEMPEG + NIVO增加了所有检测的免疫细胞亚群计数，包括调节性T细胞。随后，在联合治疗组的后续治疗周期中，CD8 + T细胞、传统CD4 + T细胞及全身干扰素γ水平的升高出现衰减。各治疗组之间肿瘤生物标志物的变化相当。这些生物标志物结果有助于更好地理解BEMPEG + NIVO的作用机制，并可能有助于解释PIVOT IO 001的临床观察结果。
