Fecal Microbiota Transplant + Anti-PD-1 Therapy for Metastatic Colorectal Cancer

Overseen By Michael J Overman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-PD-1 therapy

Must not be taking: Live vaccines, Immunosuppressants

Disqualifiers: Ileostomy, Colostomy, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 15

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for metastatic colorectal cancer using a combination of fecal microbiota transplants and anti-PD-1 therapy, such as pembrolizumab or nivolumab. The goal is to assist patients whose cancer did not respond to previous anti-PD-1 treatments. Researchers aim to enhance the effectiveness of immunotherapy by adding healthy bacteria from fecal transplants. Individuals with metastatic colorectal cancer, who have not responded to similar treatments and have specific tumor characteristics, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any systemic anti-cancer therapy within 2 weeks of starting the study treatment, except for ongoing nivolumab or pembrolizumab therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplants (FMT) are generally safe and feasible. Most side effects reported in studies are mild to moderate, such as stomach upset or diarrhea. Pembrolizumab and nivolumab, already approved for other uses, are usually well-tolerated. Serious side effects can occur but are uncommon. The combination of FMT with these treatments aims to enhance the immune system's ability to fight cancer. Studies so far suggest this combination is safe, with mostly manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic colorectal cancer because they combine fecal microbiota transplant (FMT) with immune checkpoint inhibitors like pembrolizumab and nivolumab. Most treatments for this cancer focus solely on targeting cancer cells directly, but these investigational treatments aim to enhance the body's immune response by altering gut bacteria, potentially boosting the effectiveness of immune therapies. This novel approach could offer a new avenue of hope for patients who haven't responded well to traditional chemotherapy and standard immunotherapy alone.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

This trial will evaluate the combination of fecal microbiota transplant (FMT) with anti-PD-1 therapies, specifically pembrolizumab and nivolumab, for metastatic colorectal cancer. Studies have shown that combining FMT with anti-PD-1 therapy may enhance treatment response in cancer patients. FMT involves transferring healthy gut bacteria to patients, potentially boosting the effectiveness of cancer treatments. In this trial, one group of participants will receive FMT along with pembrolizumab, and previous research indicates that this combination has led to better progression-free survival rates. Another group will receive FMT combined with nivolumab, which has shown promise in improving treatment responses for those who did not initially respond to immune checkpoint inhibitors. These findings suggest that FMT might be a promising approach to improving outcomes for patients with advanced colorectal cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael J Overman, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal cancer that didn't respond to anti-PD-1 therapy. They must have a certain type of tumor (dMMR or MSI-H), good kidney and liver function, no severe allergies to pembrolizumab or nivolumab, not be pregnant, and agree to use effective contraception.

Inclusion Criteria

My cancer has spread and can be measured by scans.

My blood counts are within a healthy range.

Participant (or legally acceptable representative) must provide written informed consent for the trial

Exclusion Criteria

I don't have any health issues that could affect the study's results.

Participant must not have an ileostomy or colostomy bag

I haven't had a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Patients receive metronidazole, vancomycin, and neomycin prior to colonoscopic FMT

8 days

1 visit (in-person)

Treatment

Patients undergo colonoscopic FMT and receive pembrolizumab or nivolumab with fecal microbiota transplantation capsules

6 months

Multiple visits (in-person and virtual) every 14-21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplantation
• Nivolumab
• Pembrolizumab

Trial Overview The study tests if fecal microbiota transplants combined with pembrolizumab or nivolumab can help control metastatic colorectal cancer in patients who previously did not respond to anti-PD-1 therapies. It includes questionnaires, antibiotics before the transplant, biopsies, and follow-up assessments.

How Is the Trial Designed?

Group I: Arm II (FMT, nivolumab) Experimental Treatment 7 Interventions

Patients receive metronidazole PO Q8H on days -14 to -8 and then vancomycin PO Q6H and neomycin PO Q6H on days -8 to -6. Patients then undergo colonoscopic FMT on day -5. POST-COLONOSCOPIC FMT: Patients receive standard of care nivolumab IV over 30 minutes on day 1. Patients also receive fecal microbiota transplantation capsule PO on days 1 and 8 of cycles 1-2. Beginning in cycle 4, patients receive fecal microbiota transplantation capsule PO on day 1 of every other cycle. Cycles repeat every 14 days for up to 6 months in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (FMT, pembrolizumab) Experimental Treatment 8 Interventions

Patients receive metronidazole PO Q8H on days -14 to -8 and then vancomycin PO Q6H and neomycin PO Q6H on days -8 to -6. Patients then undergo colonoscopic FMT on day -5. POST-COLONOSCOPIC FMT: Patients receive standard of care pembrolizumab IV over 30 minutes on day 1. Patients also receive fecal microbiota transplantation capsule PO on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients receive fecal microbiota transplantation capsule PO on day 1. Cycles repeat every 21 days for up to 6 months in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The gut microbiome can predict the risk of developing immune-related adverse events (irAEs) in melanoma patients undergoing immune checkpoint blockade (ICB) therapy, with two distinct bacterial community clusters identified that show a nearly 7-fold difference in risk.

Specific bacterial strains, such as Bacteroides dorei in the high-risk group and Bacteroides vulgatus in the low-risk group, were linked to the likelihood of developing irAEs, suggesting that the gut microbiome composition may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma. Usyk, M., Pandey, A., Hayes, RB., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001471

Fecal microbiota transplantation to enhance cancer ... These results suggest that FMT may improve chemotherapy efficacy and survival outcomes in patients with upper gastrointestinal malignancies and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9589549/

Cancer Immunotherapy: Fecal Microbiota Transplantation ... Fecal microbiota transplantation in patients who fail to respond to immune checkpoint inhibitors is expected to produce better prognosis for patients.

3. cell.com cell.com/cell-host-microbe/fulltext/S1931-3128(24)00228-2

Fecal microbiota transplantation improves anti-PD-1 ... These outcomes, representing an objective response rate of 7.7% (1/13) and a disease control rate of 46.2% (6/13), underscore the combined ...

4. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04183-y

Microbiota boost immunotherapy? A meta-analysis dives into ... As for FMT methods, oral fecal microbiota capsules appeared to be more effective (ORR: 49%) compared to endoscopic delivery (ORR: 34%) or ...

5. withpower.com withpower.com/trial/fecal-microbiota-transplant-anti-pd-1-therapy-for-metastatic-colorectal-cancer-e2b58

Fecal Microbiota Transplant + Anti-PD-1 Therapy for ... What data supports the effectiveness of the treatment Fecal Microbiota Transplantation combined with anti-PD-1 therapy for metastatic colorectal cancer?

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04729322

Fecal Microbiota Transplant and Re-introduction of Anti-PD ... This phase II trial studies the effect of fecal microbiota transplant and re-introduction of anti-PD-1 therapy (pembrolizumab or nivolumab) in treating ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7325521/

Immunotherapy in Colorectal Cancer: Potential of Fecal ... This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota- ...

8. touchoncology.com touchoncology.com/gastrointestinal-cancers/journal-articles/modulating-cancer-immunotherapy-through-the-intestinal-microbiota-mechanisms-clinical-evidence-and-the-emerging-role-of-faecal-microbiota-transplantation/

Modulating Cancer Immunotherapy Through the Intestinal ... A safety trial of FMT therapy in combination with antibacterial agents for patients with cancer undergoing ICI is currently under way, and this ...