Preoperative Pembrolizumab Plus Bevacizumab Combined With Chemotherapy in Patients With pMMR/MSS Locally Advanced Colorectal Cancer
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ABSTRACT: This prospective, single-arm study aims to investigate the safety and efficacy of pembrolizumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS locally advanced colorectal cancer patients
Project description:In this open-label phase II study, patients will be scheduled for neoadjuvant treatment with PD-1 antibody following preoperative Chemoradiotherapy with capecitabine for pMMR/MSS rectal cancer staged as locally advanced (cT3-T4N+/-M0 for rectal cancer). This treatment will be given during the window period until surgical resection of the tumor.
Project description:This prospective, single-arm study aims to investigate the safety and efficacy of Nivolumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS Colorectal cancer liver metastases patients
Project description:This prospective, single arm study aims to evaluate the preoperative neoadjuvant safety of Sintilimab combined with XELOX plus bevacizumab in colorectal patients with liver metastasis and pMMR/MSS status.
Project description:For locally advanced rectal cancer, the initial goal of neoadjuvant chemoradiotherapy is to reduce local recurrence, but the pathologic complete response (PCR) rate is low, and distant metastasis becomes the main treatment failure pattern. With the gradual optimization of neoadjuvant chemotherapy regimens, the tumor regression efficacy in patients has improved, leading to increased organ preservation and reduced distant metastasis. Therefore, neoadjuvant treatment for locally advanced rectal cancer has transitioned from an era focused on local control of recurrence to an era focused on improving tumor regression, organ preservation, and long-term survival. Thus, there is a trend towards intensifying the whole course of neoadjuvant treatment for rectal cancer to preserve organ function. The combination of chemotherapy, immunotherapy, and radiotherapy is currently the most powerful approach to maximize tumor regression and achieve organ preservation in low rectal cancer. Currently, several clinical studies on the use of PD-1 inhibitors in combination with preoperative chemoradiotherapy for locally advanced rectal cancer are ongoing internationally, with the majority focusing on PD-1 monotherapy or PD-1 combined with the CapOX regimen in combination with synchronous chemoradiotherapy as neoadjuvant treatment. However, there is no specific research reported on the use of PD-1 combined with FOLFOXIRI regimen in combination with synchronous chemoradiotherapy as a whole course neoadjuvant treatment for pMMR (proficient mismatch repair) locally advanced rectal cancer. Based on the above evidence from evidence-based medicine, we plan to conduct a phase II prospective clinical study to explore the efficacy and treatment safety of PD-1 monoclonal antibody and FOLFOXIRI chemotherapy combined with intensity-modulated radiotherapy as a whole course neoadjuvant treatment in pMMR locally advanced low rectal cancer. The results of this study may open up new treatment approaches for optimizing whole course neoadjuvant chemotherapy in locally advanced rectal cancer and provide a novel treatment strategy for organ preservation in pMMR rectal cancer.
Project description:Explore the efficacy of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer patients; To evaluate the safety and tolerability of radiotherapy combined with Tislelizumab and irinotecan in MSS/pMMR inoperable recurrent and metastatic colorectal cancer; To evaluate the radiosensitization effects of Tslelizumab and irinotecan;
Project description:gene expression profiling of locally invasive breast carcinomas treated with preoperative radiotherapy the purose of this study was to establish molecular signature associated with response to radiotherapy using radiotherapy-naïve biopsies of locally advanced breast cancer
Project description:This is an open-label phase II study, with the aim of investigating the efficacy and safety of Tislelizumab + Fruquintinib combination therapy in ARID1A-mutated pMMR/MSS metastatic colorectal cancer who have been treated with standard chemotherapy that includes fluoropyrimidine, oxaliplatin, and irinotecan. Patients with hypermutated CRC that carries POLE/POLD1 mutations cannot be included.
Project description:Glioblastoma is immunologically “cold” and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we performed bulk-RNA seq on resected tumor tissue in an additional 25 patients with surgically-accessible recurrent glioblastoma. Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.