第四阶段转移性结直肠癌患者的临床试验

临床试验对话
英雄符号

For this month’s Clinical Trials Conversations, we’re diving into trials in the first-line therapy for people with stage IV metastatic colorectal cancer (mCRC). First-line therapy is defined as the first-therapy given after a diagnosis of colorectal cancer. In this blog, we’re exploring first line therapy specifically for patients with mCRC.

Maia,你能告诉我们一些针对即将接受一线治疗的转移性CRC患者的临床试验,我们应该讨论一下吗?

我想强调的第一个试验是 NCT03953235:"基于新抗原的治疗性癌症疫苗,与免疫检查点阻断相结合(GO-005)"。

This clinical trial, ongoing at several locations nationwide, recruits microsatellite stability (MSS) CRC patients who are receiving first-line (1L) therapy for mCRC —and also those who received that firstline for mCRC and progressed on it, but who have not received the following line. 

在这项试验中,具有某些突变的患者接受两种或三种免疫疗法的联合治疗:一种主要/增强型治疗疫苗(称为GRT-C903/GRT-R904),它针对共享的新抗原;一种抗PD-1(检查点抑制剂Nivolumab);以及在某些情况下,一种抗CTLA-4(检查点抑制剂Ipilimumab)。

目标突变是:

癌症患者
CTNNB1_S37F 
CTNNB1_S45F 
CTNNB1_S45P 
CTNNB1_T41A 
ERBB2_Y772_A775dup 
KRAS_G12C或NRAS_G12C 
KRAS_G12D或NRAS_G12D 
kras_g12v / kras_g13d 
KRAS_Q61H或NRAS_Q61H 
KRAS_Q61K或NRAS_Q61K 
KRAS_Q61L或NRAS_Q61L 
KRAS_Q61R或NRAS_Q61R 
TP53_K132E 
TP53_K132N 
TP53_R213L 
TP53_R249M 
TP53_S127Y

新抗原是由于在肿瘤细胞的DNA中发现突变而产生的小蛋白片段。它们在正常细胞中是不存在的。这些新的("新")抗原对T细胞来说是陌生的,所以如果T细胞认为它们是危险的,它们就有可能引起非常强烈的反应。共享的新抗原是那些已知或预计在一个患者子集中常见的新的、变异的抗原。

针对这些新抗原的疫苗旨在利用它们来激活身体的抗肿瘤免疫反应,以消除癌细胞。

欲了解更多细节(关于设计、资格、地点等),请查看 临床试验记录 and preliminary 报告 from this trial.

我想强调的下一个审判是 NCT04714983: * Intra-tumoral (liver lesions) injections of oncolytic adenovirus called DNX-24

Several clinical trials are investigating the addition of immunotherapy, perioperatively (before or after surgery), with the idea of re-engaging the immune system itself to prevent recurrence.

Too often, patients are not aware of these options because of incorrect ideas about clinical trials (“clinical trials are a last resource";  “they are always alternative to standard of care” —instead of a complement, sometimes). Also, it’s unlikely that patients know such trials exist when the studies are not offered at the facility where they are being treated.

一个以治愈性肝切除为目标的IV期患者可能要考虑防止复发的方案,尽管之前和/或标准护理提供的 "拖 "化疗,有时还是会发生复发。 

其中一项是小型试验(在佛罗里达州坦帕市的莫菲特癌症中心)。它实施一种实验性免疫疗法(一种溶瘤病毒:一种 "破坏癌症的病毒"),在手术前以两次注射的形式直接注入肝脏肿瘤。就是说:它适用于刚刚接受一线(1L)治疗的转移性患者。

"The purpose of this study is to test an experimental oncolytic adenovirus called DNX-2440 in patients with resectable multifocal (≥ 2 lesions) liver metastasis, who are scheduled to have curative-intent liver resection surgery.” Patients will receive two consecutive intra-tumoral (meaning within the tumor) injections of DNX-2440 into a metastatic liver lesion prior to surgery for liver resection. The agent was developed by researchers at MD Anderson Cancer Center in Houston, Texas, and is also in trials for a difficult to treat brain cancer (glioblastoma). Learn more about 本审判.

这很有见地,马亚。曼珠,你认为哪些试验对我们的社区来说是有趣的,可以了解一下?

第一个是BREAKWATER,为那些有 BRAF V600e mutation and who have mCRC.This international trial with over 77 locations is to find out whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes compared to current standard of care (SOC) chemotherapy in patients with BRAF V600E-mutant mCRC who have not started any treatment yet. Though the BEACON doublet combination (encorafenib —a BRAF inhibitor— and cetuximab —an antibody targeting EGFR) works well for a large number of patients with a BRAF V600e mutated tumors, sooner or later resistance clones (these are groups of tumor cells with other molecular alterations that may arise/get selected as a result of treatment and render the treatment ineffective) develop and the treatment may stop working. 

这项试验是为了弄清在BEACON双联剂中加入化疗是否能推迟抗性克隆的发生。 

The trial has a 60 patient safety lead-in to look at the safety and tolerability of combining chemotherapy with targeted therapy. As I understand, safety lead-in are initial cohorts of a study to figure out the safety and tolerability of new drugs/combinations being tested before large sets of patients are randomized to the trial arms. The next part of the trial usually uses the information from the safety lead-in to inform that part of the trial. In this safety lead-in, there are two cohorts 1) EC+Folfiri and 2) EC+Folfox. This will help identify the targeted therapy+chemo combination that will be used in the second part of the trial. Once 30 evaluable patients are enrolled in each cohort and complete cycle one, several parameters will be examined.  I have heard this part is done enrolling.

This trial is an effort to find out if add cohorts of a study to figure out the safety and tolerability of new drugs/combinations being tested before large sets of patients are randomized to the trial arms. The next part of the trial usually uses the information from the safety lead-in to inform that part of the trial. In this safety lead-in, there are two cohorts 1) EC+Folfiri and 2) EC+Folfox. This will help identify the targeted therapy+chemo combination that will be used in the second part of the trial. Once 30 evaluable patients are enrolled in each cohort and complete cycle one, several parameters will be 审查.  I have heard this part is done enrolling.

该试验有930名参与者,有三个试验组:

  1. 单独的EC(单独的靶向治疗)
  2. EC+Folfiri or EC+Folfox (targeted therapy+chemo)
  3. Folfox+Bev or Folfiri+Bev or Folfoxiri+Bev or Capox+Bev (SOC Chemo+biological arm)

我真的很期待安全引导试验的结果。我们非常需要对BRAF突变的CRC进行试验,因为这是一种非常具有侵略性的疾病,而像这项试验这样将化疗与靶向治疗相结合的方法可能有助于将疾病控制在较长一段时间内。如果这种组合的安全性和耐受性是可控的,也许类似的方法也可以尝试用于KRAS突变的CRC。

要了解更多关于临床试验的信息,请务必关注我们的 博客系列 highlighting various trials each month.

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每月一次,Maia和Manju将花时间为我们的社区解读重要的研究试验、技巧和建议。请务必订阅 报名 with Fight CRC and join COLONTOWN’s online community to continue receiving the most relevant updates in the CRC world!

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