Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA.
Br J Cancer. 2021 May;124(11):1803-1808. doi: 10.1038/s41416-021-01368-z. Epub 2021 Apr 7.
MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.
This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).
A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.
Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS.
NCT03332498.
完全错配修复（pMMR）结直肠癌（CRC）通常对免疫疗法无反应。最近的数据表明，伊布替尼可能增强抗 PD-1 免疫疗法的抗肿瘤活性。在这项研究中，我们评估了伊布替尼联合帕博利珠单抗在难治性转移性 pMMR CRC 中的安全性和疗效。
这是一项在难治性转移性 pMMR CRC 患者中进行的 1/2 期研究。1 期和 2 期的主要终点分别为最大耐受剂量（MTD）和疾病控制率。次要终点为安全性、无进展生存期（PFS）和总生存期（OS）。
共纳入 40 例患者。未观察到剂量限制毒性，也未确定 MTD。伊布替尼的最高测试剂量为 560mg，每日一次，与每 3 周一次的固定剂量帕博利珠单抗 200mg 联合用于 2 期部分。最常见的 3/4 级治疗相关不良事件是贫血（21%）、疲劳（8%）和碱性磷酸酶升高（8%）。在 31 例可评估患者中，8 例（26%）病情稳定，未观察到客观缓解。中位 PFS 和 OS 分别为 1.4 和 6.6 个月。
伊布替尼 560mg 每日一次联合帕博利珠单抗 200mg 每 3 周一次在转移性 CRC 中耐受性良好，抗肿瘤活性有限。临床试验。
NCT03332498。
