LND101 + Immune Checkpoint Blockade for Melanoma

(Canbiome2 Trial)

Recruiting at 3 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

Trial Summary

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.

What data supports the effectiveness of the treatment LND101 + Immune Checkpoint Blockade for melanoma?

Immune checkpoint blockade, particularly targeting PD-1 and PD-L1, has shown significant promise in treating metastatic melanoma, with drugs like nivolumab and pembrolizumab demonstrating antitumor activity and acceptable safety in clinical trials. ^{1 2 3 4 5}

What safety data exists for LND101 + immune checkpoint blockade treatment for melanoma?

Immune checkpoint inhibitors, like those used in combination with LND101, can cause side effects due to immune system activation, including skin issues like itching and rashes, and more serious conditions like toxic epidermal necrolysis (a severe skin reaction). These treatments can also affect the gastrointestinal tract, liver, and endocrine systems, leading to symptoms like nausea, diarrhea, and thyroid problems. While these side effects are a concern, they are a known part of how these treatments work. ^{6 7 8 9 10}

How is the drug LND101 + Immune Checkpoint Blockade different from other melanoma treatments?

LND101 combined with immune checkpoint blockade is unique because it targets the LAG-3 pathway, a new checkpoint in melanoma treatment, alongside the established PD-1 pathway. This combination has shown impressive effectiveness with fewer side effects compared to traditional PD-1 and CTLA-4 inhibitors, making it a promising first-line therapy for metastatic melanoma. ^{3 5 11 12 13}

What is the purpose of this trial?

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 for Fecal Microbiota Transplant (FMT) in addition to the usual immunotherapy treatment called Immune Checkpoint Blockade (ICB)? FMT treatment changes the bacteria in your gut called the microbiome.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Relatlimab and nivolumab in the treatment of melanoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

PD-1 and PD-L1 antibodies for melanoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Therapy in Melanoma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Immune-Mediated Toxic Epidermal Necrolysis. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Events in Patients With Advanced Melanoma: A Systematic Review and Network Meta-analysis. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-risk Resected Melanoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Warming "Cold" Melanoma with TLR9 Agonists. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Durable Responses to Anti-PD1 and Anti-CTLA4 in a Preclinical Model of Melanoma Displaying Key Immunotherapy Response Biomarkers. [2022]