LND101 + Immune Checkpoint Blockade for Melanoma

(Canbiome2 Trial)

Recruiting at 13 trial locations

Overseen By Janet Dancey

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Antibiotics, Corticosteroids, Anticancer therapy, others

Disqualifiers: Concurrent malignancy, Brain metastases, Autoimmune disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new treatment, LND101, can stop melanoma (a type of skin cancer) from growing or spreading. The trial adds LND101 to the usual treatment, immune checkpoint blockade (ICB), which helps the immune system fight cancer. LND101 alters gut bacteria through a process known as a fecal microbiota transplant (FMT). Individuals with stage IV melanoma or advanced melanoma that cannot be surgically removed, who have not yet received ICB treatment for their advanced disease, 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 of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received antibiotics within 14 days of enrollment, and you must not be on systemic corticosteroids over 10mg per day. It's best to discuss your specific medications with the trial team.

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

Research has shown that LND101, when combined with treatments like nivolumab and pembrolizumab, has an acceptable safety profile. These treatments are known for their strong tumor-fighting abilities and are usually well-tolerated. Although limited information exists about LND101 alone, its safety is still under study in the ongoing trial phase. However, using it with these FDA-approved treatments for different uses offers some reassurance about its potential safety in humans. It is important to consult a doctor before joining a trial to understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

LND101 is unique because it introduces a novel approach by combining a bowel preparation and a single-dose treatment with the existing standard-of-care immune checkpoint blockade (ICB) therapies. While traditional treatments for melanoma focus on immune checkpoint inhibitors like pembrolizumab or nivolumab, LND101 aims to enhance the effectiveness of these treatments potentially by altering the gut microbiota, which may play a role in the immune response. Researchers are excited about this treatment as it could offer a new way to boost the body's ability to fight melanoma, potentially leading to better outcomes for patients.

What evidence suggests that LND101 for FMT combined with ICB could be effective for melanoma?

In this trial, participants will receive either the standard-of-care immune checkpoint blockade (ICB) treatment or a combination of LND101 with standard-of-care ICB. Studies have shown that LND101, when combined with a treatment that aids the immune system in attacking cancer cells, can improve outcomes for patients with advanced melanoma. Specifically, a previous study found this combination treatment to be both safe and effective, with 65% of patients experiencing tumor shrinkage or halted growth. Research suggests that LND101 may enhance the effectiveness of immune treatments by altering gut bacteria. These findings indicate that LND101 could potentially reduce the risk of melanoma growing or spreading when added to standard immune therapy. ^{1 2 3 6 7}

Who Is on the Research Team?

Arielle Elkrief

Principal Investigator

CHUM-Centre Hospitalier de ''Universite de Montreal, Montreal, QC Canada

John Lenehan

Principal Investigator

London Regional Cancer Program, London, ON Canada

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma who haven't had immune checkpoint blockade (ICB) therapy for their condition, or if they did, it was over 6 months ago. They can join if they've recovered from previous treatments like BRAF/MEK inhibitors or radiation and have measurable disease. Major surgery must be at least two weeks prior.

Inclusion Criteria

I have been diagnosed with skin melanoma or melanoma with an unknown primary origin.

I had radiation therapy over a week ago and have mostly recovered from its side effects.

Participants must have measurable disease as per RECIST 1.1/ iRECIST

Exclusion Criteria

I have cancer that has spread to the lining of my brain and spinal cord.

I have not taken antibiotics in the last 14 days.

I take more than 10mg of corticosteroids daily.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LND101 for Fecal Microbiota Transplantation in combination with Immune Checkpoint Blockade

6-8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LND101

Trial Overview The study tests whether adding LND101 to standard ICB treatment improves outcomes in advanced melanoma patients. LND101 involves fecal microbiota transplantation (FMT), which alters gut bacteria, potentially affecting the immune system's response to cancer.

How Is the Trial Designed?

Group I: LND101 for FMT + Standard-of-care ICB Experimental Treatment 2 Interventions

Bowel preparation; LND101(single-dose); Assigned single agent or combination ICB treatment.

Group II: Standard-of-care ICB Active Control 1 Intervention

Assigned single agent or combination ICB treatment

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

The Weston A. Price Foundation

Collaborator

Trials

4

Recruited

440+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Weston Family Foundation

Collaborator

Trials

4

Recruited

290+

Weston Family Foundation

Collaborator

Published Research Related to This Trial

In a study of 66 patients with advanced melanoma treated with PD-1 antibodies, those with elevated baseline serum lactate dehydrogenase (LDH) had significantly shorter overall survival compared to those with normal LDH levels, indicating that LDH can be a critical prognostic marker.

Changes in LDH levels during treatment were predictive of response; patients with a reduction in LDH were more likely to achieve partial remission, while those with an increase had a shorter overall survival, suggesting LDH could help monitor treatment effectiveness early on.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Diem, S., Kasenda, B., Spain, L., et al.[2022]

Nivolumab and pembrolizumab, two anti-PD-1 antibodies, have demonstrated significant antitumor activity and acceptable safety profiles in patients with metastatic melanoma during early clinical trials.

Ongoing Phase III studies are further evaluating the efficacy and safety of anti-PD-1 therapies, including promising results from combinations with other treatments like anti-CTLA-4 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. Simeone, E., Grimaldi, AM., Ascierto, PA.[2023]

The combination of LAG-3 and PD-1 blockade, specifically using relatlimab and nivolumab, is being investigated as a promising new treatment approach for melanoma.

Two clinical trials have been conducted to evaluate the effectiveness of this combination therapy in patients with metastatic and high-risk, node-positive melanoma, indicating a potential advancement in melanoma treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relatlimab and nivolumab in the treatment of melanoma. Au, L., Larkin, J., Turajlic, S.[2023]

In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.

Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]

Inhibition of immune checkpoints using PD-1 and CTLA-4 monoclonal antibodies has significantly improved treatment options for advanced-stage melanoma and other cancers, with FDA approval for their use in metastatic melanoma.

While these immunotherapies are effective, they can cause a range of immune-related adverse events, particularly affecting the skin, gastrointestinal tract, liver, and endocrine systems, necessitating careful management of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Boutros, C., Tarhini, A., Routier, E., et al.[2022]

Citations

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

Improved survival in advanced melanoma patients treated ... Combination therapy was safe, and the objective response rate (ORR) was 65%. We now report survival data based on over 3 years of follow-up.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06623461

Study Details | NCT06623461 | LND101 for Fecal ... This study is being done to answer the following question: Can the chance of melanoma growing or spreading be lowered by receiving a treatment called LND101 ...

3. withpower.com withpower.com/trial/phase-2-melanoma-11-2024-bc406

LND101 + Immune Checkpoint Blockade for Melanoma Trial Overview The study tests whether adding LND101 to standard ICB treatment improves outcomes in advanced melanoma patients. LND101 involves fecal microbiota ...

4. ctg.queensu.ca ctg.queensu.ca/public/melanoma/melanoma-disease-site

Melanoma Disease Site | Canadian Cancer Trials Group This trial hypothesizes that intermittent PD-1 inhibitor treatment, following maximum benefit on initial treatment, is no worse for survival compared to ...

5. ecancer.org ecancer.org/en/news/26082-world-first-clinical-trial-will-study-specialised-pills-to-improve-treatment-of-advanced-pancreatic-cancer

World first clinical trial will study specialised pills to improve ... “Earlier studies led by Lawson and LHSCRI have demonstrated that the treatment is safe in other cancers and appears to result in better ...

6. rupress.org rupress.org/jem/article/222/7/e20250378/277403/Microbiota-centered-interventions-to-boost-immune

Microbiota-centered interventions to boost immune ... We highlight how the gut microbiome modulates immune checkpoint blockade efficacy in cancer. We outline diagnostic tools for dysbiosis, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11670468/

Current trends in sensitizing immune checkpoint inhibitors for ... Leveraging big data of immune checkpoint blockade response identifies novel potential targets. ... melanoma: safety run-in and biomarker ...