Perioperative treatment and biomarker analysis of LP002, an anti-PD-L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer

IF 3.1 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2022-11-07 DOI:10.1002/cam4.5414

Jia-lin Tang, Bo Zhang, Jian-ping Xu, Ling Qi, Dao Xin, Lin Wang, Bing-zhi Wang, Yan-tao Tian, Yong Li, Jing Huang

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引用次数: 1

Abstract

Background

The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer.

Methods

We enrolled patients with resectable and PD-L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5-fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin-free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next-generation sequencing (NGS) with pre- and post-treatment tumor samples.

Results

Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow-up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty-four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1–3, including one achieving pCR. Twenty-seven patients had treatment-related adverse events (TRAEs), while grade 3–4 TRAEs were observed in 11 patients. No treatment-related deaths occurred. MIF staining revealed that TRG 1–3 group was associated with a higher density of PD-L1+/CD68+ cells in the pre-treatment tumor parenchyma than TRG 4–5 group (p = 0.048). NGS studies with paired pre- and post-treatment tumor samples revealed the disappearance of pre-existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1–3 (p = 0.0313).

Conclusions

LP002 plus cisplatin and 5-fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.

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抗pd - l1抗体LP002加化疗在可切除胃癌和胃食管结癌的围手术期治疗和生物标志物分析

背景在可手术胃或胃食管交界处(GEJ)癌围手术期化疗中加入免疫检查点抑制剂已成为研究热点之一，但缺乏可靠的疗效生物标志物。我们进行了一项i期试验，以评估LP002(一种抗pd - l1抗体)加化疗作为胃癌或胃癌围手术期治疗的安全性和有效性。方法我们招募了可切除和PD-L1阳性的胃癌或胃癌患者。符合条件的患者接受术前3个周期、术后6个周期的LP002顺铂+ 5-氟尿嘧啶静脉注射，每2周重复一次。主要终点是安全性。次要终点包括无切缘(R0)切除率和病理完全缓解(pCR)。我们还利用多重免疫荧光(MIF)染色和新一代测序(NGS)对治疗前和治疗后的肿瘤样本进行了表征。结果入选30例患者，其中28例为GEJ癌。中位随访7.9个月，所有患者完成术前治疗，27例患者接受手术治疗。24例患者行R0切除术。6例(20.0%)达到标准肿瘤消退等级(TRG) 1-3，其中1例达到pCR。27例患者出现治疗相关不良事件(TRAEs)， 11例患者出现3-4级TRAEs。无治疗相关死亡发生。MIF染色显示，TRG 1-3组治疗前肿瘤实质中PD-L1+/CD68+细胞密度高于TRG 4-5组(p = 0.048)。配对治疗前后肿瘤样本的NGS研究显示，术前LP002和化疗后，原有突变消失，新突变出现，突变丰度发生变化。同时，TRG 1-3组患者的肿瘤突变负担降低(p = 0.0313)。结论LP002联合顺铂和5-氟尿嘧啶用于胃癌或胃癌患者是安全的，未来需要通过适当的生物标志物进行患者选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.