The goal of this clinical trial is to verify the effectiveness and safety of Lactobacillus johnsonii in combination with CapeOX and Pembrolizumab for the treatment of MSS/pMMR metastatic colorectal cancer (CRC). The main questions it aims to answer are: ① To verify the effectiveness of Lactobacillus johnsonii in the treatment of MSS/pMMR type metastatic colorectal cancer (mCRC) who have failed the standard regimen of chemotherapy; ② To explore the safety of Lactobacillus johnsonii in the treatment of MSS/pMMR type metastatic colorectal cancer (mCRC) who have failed the standard regimen of chemotherapy. Participants who meet all the inclusion criteria will be enrolled in the study and randomly assigned in a 1:1 ratio to either the CapeOX + Pembrolizumab + placebo group or the CapeOX + Pembrolizumab + Lactobacillus johnsonii group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
150
It is previously reported Lactobacillus johnsonii #CGMCC29884 in Cell. Animal studies showed it combined with Clostridium sporogenes to produce indolepropionic acid, modulating CD8+ T cell immune quiescence in the tumor microenvironment and sensitizing immunotherapy in CRC, breast cancer, and melanoma. Mager et al. found Lactobacillus johnsonii enhanced CTLA-4 mAb antitumor effects in CRC mouse models. Studies showed it's a typical probiotic widely distributed in various hosts' guts and has long been applied in food and feed industries. Preclinical studies indicated it improved memory through the gut-brain axis, had anti-inflammatory and antibacterial effects, and regulated metabolic diseases. Randomized trials found it effectively inhibited Helicobacter pylori colonization without obvious adverse reactions, suggesting it's a potentially safe and effective treatment.
Placebo
Progression-Free Survival (PFS)
Progression-Free Survival (PFS), as per RECIST 1.1 criteria, assessed by blinded independent review, is defined as the time from randomization to the occurrence of tumor progression or death from any cause, whichever comes first, up to 24 months.
Time frame: from randomization to the occurrence of tumor progression or death from any cause, whichever comes first, up to 24 months.
Objective Response Rate, ORR
Objective Response Rate (ORR) is defined as the proportion of patients who achieve either a Complete Response (CR) or a Partial Response (PR), as determined by blinded independent review according to RECIST 1.1 criteria.
Time frame: from enrollment to the end of treatment, up to 24 months.
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