Phase II Study of Pembrolizumab Plus Capecitabine and Bevacizumab for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer

IF 2.7 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2026-06-01 Epub Date: 2026-02-18 DOI:10.1016/j.clcc.2026.02.003

Andrea Bocobo , Julia Whitman , Bridget P. Keenan , Kelvin L. Koser , Wesley A. Kidder , Sorbarikor Piawah , Katherine Van Loon , Spencer C. Behr , K. Pallav Kolli , Xiaoying Chen , Courtney Onodera , Manjusha Pande , Marin Pollak , Renee Wang , Joel Babdor , Matthew H. Spitzer , Li Zhang , Lawrence Fong , Chloe E. Atreya

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引用次数: 0

Abstract

Background

This study evaluated the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Patients and Methods

Patients with MSS/pMMR mCRC with stable or progressive disease on at least 1 prior fluoropyrimidine-based therapy received capecitabine 1000 mg/m² by mouth twice daily days 1 to 14, bevacizumab 7.5 mg/kg day 1, and pembrolizumab 200 mg day 1 every 3 weeks. The primary endpoint was overall response rate by RECIST 1.1. Secondary endpoints were safety, duration of response, progression-free survival (PFS), and overall survival (OS).

Results

Forty-four patients were enrolled between April 2018 and October 2021. Median follow up time was 9.3 months, while median time on treatment was 6 months. Overall response rate for 40 evaluable patients was 5% with median duration of response of 13.5 months. Median PFS was 4.1 months, and median OS was 10.1 months. Grade ≥ 3 treatment related adverse events occurred in 13 patients (30%); none were classified as immune-related. Grade 1 to 2 immune-related adverse events occurred in 8 patients (18%). Dose modifications occurred in 27 patients (61%), most commonly for palmar-plantar erythrodysesthesia. Single cell RNA sequencing on a subset of tumor biopsies demonstrated that the frequency of dendritic cells and tumor-infiltrating activated T cells correlated with time on treatment.

Conclusions

The combination of pembrolizumab with capecitabine and bevacizumab was tolerable with an expected toxicity profile in MSS/pMMR mCRC patients. The overall response rate of 5% did not meet the prespecified target of ≥ 15%; however, 55% patients remained on treatment > 6 months.

ClinicalTrials.gov Identifier: clinicaltrials.gov: NCT03396926.

查看原文本刊更多论文

派姆单抗联合卡培他滨和贝伐单抗治疗微卫星稳定/错配修复精通转移性结直肠癌的II期研究

背景：本研究评估了派姆单抗联合卡培他滨和贝伐单抗治疗微卫星稳定（MSS）转移性结直肠癌（mCRC）的安全性、耐受性和初步疗效。患者和方法：疾病稳定或进展的MSS/pMMR mCRC患者既往至少接受1次氟嘧啶治疗，接受卡培他滨1000mg /m2口服，每日2次，第1至14天，贝伐单抗第1天7.5 mg/kg，每3周派姆单抗第1天200mg。主要终点是RECIST 1.1的总缓解率。次要终点是安全性、反应持续时间、无进展生存期（PFS）和总生存期（OS）。结果：44名患者在2018年4月至2021年10月期间入组。中位随访时间9.3个月，中位治疗时间6个月。40例可评估患者的总缓解率为5%，中位缓解持续时间为13.5个月。中位PFS为4.1个月，中位OS为10.1个月。13例患者发生≥3级治疗相关不良事件（30%）；没有一个被归类为免疫相关。8例患者（18%）发生1至2级免疫相关不良事件。27例（61%）患者发生剂量改变，最常见的是掌跖红肿。肿瘤活检的一个子集的单细胞RNA测序表明，树突状细胞和肿瘤浸润活化T细胞的频率与治疗时间相关。结论：在MSS/pMMR mCRC患者中，派姆单抗联合卡培他滨和贝伐单抗是可耐受的，并且具有预期的毒性。5%的总有效率未达到≥15%的预定目标；然而，55%的患者在6个月后仍在接受治疗。临床试验：gov标识符：Clinicaltrials .gov: NCT03396926。

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

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.