FMT + Immunotherapy for Non-Small Cell Lung Cancer or FMT + Immunotherapy for Melanoma

(FMT-LUMINATE Trial)

Not currently recruiting at 7 trial locations

Overseen By Arielle Elkrief, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Antibiotics, Probiotics, Corticosteroids

Disqualifiers: Pregnancy, Immunodeficiency, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating advanced or hard-to-remove lung cancer and melanoma. It combines immune checkpoint inhibitor (ICI) therapy, which helps the immune system attack cancer, with fecal microbial transplantation (FMT, or stool transplant), which aims to improve gut health and possibly boost the immune response. Suitable participants include those with stage IV or metastatic melanoma or non-small cell lung cancer (NSCLC) who have not received certain treatments before and can ingest capsules. The study aims to determine if the combination can shrink tumors more effectively than current treatments. As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people.

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 use probiotics during the treatment and must stop them at least 24 hours before starting. Also, you cannot have used antibiotics within 2 weeks before joining the study.

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

Research has shown that combining fecal microbial transplantation (FMT) with immune checkpoint inhibitors (ICIs) is generally safe for patients. In studies, patients receiving FMT along with ICIs such as pembrolizumab, ipilimumab, and nivolumab demonstrated promising results with manageable side effects.

For FMT, some individuals might experience mild digestive issues, but serious problems are rare. When combined with ICIs, the treatment has been well-tolerated, with no unexpected or severe side effects reported. ICIs are already used to treat various cancers, and their side effects are well-known and closely monitored.

In summary, research suggests that the combination of FMT and ICIs is safe for cancer patients, with side effects being mostly mild and expected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining fecal microbial transplantation (FMT) with immunotherapy for non-small cell lung cancer and melanoma because it offers a novel approach to boosting the body's immune response. Unlike standard treatments that rely solely on immune checkpoint inhibitors like Pembrolizumab, Ipilimumab, and Nivolumab, this approach introduces beneficial gut bacteria through FMT. This unique combination aims to enhance the effectiveness of immunotherapy by potentially improving the gut microbiome, which is believed to play a crucial role in modulating the immune system. The innovative aspect of this treatment lies in its potential to optimize the patient’s response to existing immunotherapies, potentially leading to better outcomes.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer or melanoma?

This trial will evaluate the combination of fecal microbial transplantation (FMT) with cancer immunotherapy for non-small cell lung cancer (NSCLC) and melanoma. Research has shown that combining FMT with immunotherapy may improve treatment outcomes. Participants with NSCLC will receive pembrolizumab combined with FMT, which studies suggest can improve survival rates. Meanwhile, participants with melanoma will receive a combination of ipilimumab and nivolumab with FMT, which has been associated with enhanced effectiveness and improved survival rates. The approach aims to alter gut bacteria through FMT to help the immune system fight cancer more effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Arielle Elkrief, MD

Principal Investigator

CHUM

Are You a Good Fit for This Trial?

Adults over 18 with certain types of advanced melanoma or non-small cell lung cancer (NSCLC) that haven't been treated with anti-PD1 drugs. They must understand the risks of fecal microbial transplantation (FMT), not have autoimmune diseases, active infections, severe heart conditions, or be pregnant. Participants should not be on high-dose steroids and must agree to effective contraception.

Inclusion Criteria

I have never received anti-PD1 treatment.

My condition is at stage IV or cannot be surgically removed.

My melanoma returned more than 6 months after my last immunotherapy.

Exclusion Criteria

I have an active inflammatory bowel condition.

I have not taken antibiotics in the last 2 weeks.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT).

Up to 2 years

Every 2-4 weeks depending on treatment regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbial Transplantation

Trial Overview The trial is testing the combination of FMT and immune checkpoint inhibitors (ICI) as a treatment for advanced melanoma and NSCLC. It aims to see if adding FMT can boost the anti-tumor effects of ICI therapy in patients who meet specific health criteria.

How Is the Trial Designed?

Group I: Immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT). Experimental Treatment 1 Intervention

Metastatic or advanced NSCLC: Single-agent Pembrolizumab (2 mg/kg or 200 mg every 3 weeks) in combination with investigational FMT capsules as follows: Full FMT at least 7 days prior to first cycle of Pembrolizumab. Metastatic melanoma and uveal melanoma: Combination therapy of Ipilimumab plus Nivolumab (Ipilimumab 3 mg/kg every 3 weeks and Nivolumab 1 mg/kg every 3 weeks x 4 doses, followed by Nivolumab 3 mg/kg or 240mg every 2 weeks or 6 mg/kg or 480mg every 4 weeks) in combination with investigational FMT capsules as follows: full FMT at least 7 days prior to first treatment with Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the second cycle with combination Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the third cycle of Ipilimumab plus Nivolumab.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Published Research Related to This Trial

Fecal microbiota transplantation (FMT) shows a higher response rate compared to medical therapy (MT) specifically for recurrent Clostridium difficile infections (RCDI), suggesting it may be a more effective treatment option for these patients.

However, FMT does not demonstrate a significant advantage over MT for treating primary Clostridium difficile infections (CDI), indicating that FMT should not be used universally for all CDI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials. Singh, T., Bedi, P., Bumrah, K., et al.[2023]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for dysbiosis in children, with a primary clinical remission rate of 72.9% observed after the procedure.

While most adverse events (AEs) were self-limiting and occurred shortly after FMT, the long-term efficacy of FMT decreased over time, suggesting that multiple FMTs may be necessary for recurrent conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study. Zou, B., Liu, SX., Li, XS., et al.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) was performed on 26 patients with recurrent Clostridium difficile infection, showing a 92% success rate in preventing further diarrhea or CDI relapse over a follow-up period of up to 30 months.

The procedure was found to be simple and safe, with most patients remaining free of significant diarrhea after the treatment, highlighting FMT as a promising alternative to prolonged antibiotic courses for managing recurrent CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. Kelly, CR., de Leon, L., Jasutkar, N.[2022]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

The gut microbiota plays a significant role in cancer treatment, particularly in enhancing the effectiveness of immune checkpoint inhibitors (ICIs), as shown by metagenomic profiling and murine studies.

Fecal microbiota transplantation (FMT) shows promise as a novel therapeutic strategy when combined with ICIs, although safety concerns and challenges related to pathogen transmission need to be addressed before it can be widely adopted in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Jamal, R., Messaoudene, M., de Figuieredo, M., et al.[2023]

Fecal microbiota transplantation (FMT) was successfully performed in two immunocompromised children with refractory diarrhea, leading to symptom remission without any infectious complications.

The procedure resulted in the reconstruction of a diverse microbiota, indicating that FMT is a safe and effective treatment option for managing diarrhea in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. Zhong, S., Zeng, J., Deng, Z., et al.[2020]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359429/

Improved survival in advanced melanoma patients treated ... Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40759441/

Improved survival in advanced melanoma patients treated ... Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti ...

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

Fecal microbiota transplantation to enhance cancer ... We hypothesize that donor FMT may enhance treatment efficacy by altering the composition and metabolic activity of the gut microbiota, thereby ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04951583

NCT04951583 | Fecal Microbial Transplantation Non- ... The OS for patients with metastatic melanoma is now 52% at five years with combination therapy of anti-CLTA-4 (Ipilimumab) and anti-PD-1 (Nivolumab). However, ...

5. science.org science.org/doi/10.1126/science.abf3363

Fecal microbiota transplant overcomes resistance to anti– ... Our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05502913

Fecal Microbiota Transplantation With Immune Checkpoint ... This study aims to investigate the safety and efficacy of FMT treatment combined with first-line (chemo-)immunotherapy in metastatic lung cancer. The study will ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10831174/

Fecal microbiota transplantation: no longer cinderella in ... In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour ...

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

Microbiota boost immunotherapy? A meta-analysis dives into ... This meta-analysis provides preliminary evidence supporting the use of FMT as a strategy to enhance the efficacy of ICIs in patients with advanced or ...

9. tlcr.amegroups.org tlcr.amegroups.org/article/download/107071/80041

Fecal microbiota transplantation plus immune checkpoint ... historical data on both FMT and ICI rechallenge safety. ... The effect and safety of immune checkpoint inhibitor rechallenge in non- small cell lung cancer.