Pembrolizumab + EDP1503 for Advanced Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Probiotics, Immunosuppressants

Disqualifiers: Immunodeficiency, Active TB, 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

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

Compensation: Varies

Number of Visits: 3

Duration: Ongoing

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding a new oral treatment, EDP1503, can enhance the effects of the standard immunotherapy drug pembrolizumab (KEYTRUDA) for individuals with advanced melanoma, a serious type of skin cancer. Participants will first take EDP1503 alone for two weeks, followed by a combination of EDP1503 and pembrolizumab. The trial is open to those with advanced melanoma, regardless of prior treatment with anti-PD1 therapy, a common cancer treatment. Participants must agree to undergo biopsies, which involve taking small tissue samples for testing. This study seeks to improve the cancer's response to treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness 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. However, you cannot be on systemic steroid therapy or immunosuppressive therapy within 7 days before starting the trial, and you should not be taking Bifidobacterium-based probiotics or pre/pro-biotics regularly.

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

Research shows that pembrolizumab is an FDA-approved treatment for advanced melanoma. It has been proven to help patients live longer and respond better compared to treatments like ipilimumab, indicating it is generally well-tolerated.

In contrast, detailed safety information for EDP1503 is limited. This trial, being in the early stages, primarily focuses on assessing how well participants tolerate the treatment. Early trials typically aim to ensure any new treatment is safe for humans before further testing.

Participants considering this trial can feel reassured that pembrolizumab is already a standard treatment, while EDP1503 is under careful safety monitoring. ^{1 2 3 4 5}

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

Researchers are excited about Pembrolizumab combined with EDP1503 for advanced melanoma because it offers a fresh approach compared to current treatments. Most standard therapies for melanoma, like single-agent immune checkpoint inhibitors, focus on blocking specific proteins to help the immune system attack cancer. In contrast, EDP1503 is an oral microbiome therapy designed to enhance the effectiveness of Pembrolizumab by modulating the gut microbiome, which can potentially boost the immune response against tumors. This combination aims to provide a more robust and sustained anti-cancer effect, particularly for patients who have not responded well to other treatments.

What evidence suggests that this trial's treatments could be effective for advanced melanoma?

Research has shown that pembrolizumab, one of the treatments in this trial, effectively treats advanced melanoma. After ten years, 34% of patients with advanced melanoma who received pembrolizumab were still alive, compared to 23.6% of those who received a different treatment. This underscores the benefit of pembrolizumab.

The trial is studying the combination treatment with EDP1503 to determine if it can enhance pembrolizumab's effectiveness. EDP1503 is believed to strengthen the body's immune response against cancer. Early studies suggest that EDP1503 is generally well tolerated, but more research is needed to fully understand its potential when used with pembrolizumab. ^{1 5 6 7 8}

Who Is on the Research Team?

Jason Luke, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma that can't be surgically removed or has spread. Participants must have measurable disease, may or may not have had prior PD1/L1 antibody treatment depending on the cohort, and should not have received CTLA4 antibodies in a metastatic setting. They need to function well daily (ECOG 0-1) and show good organ function.

Inclusion Criteria

Be willing and able to provide written informed consent/assent for the trial.

Absolute neutrophil count (ANC) ≥1,500 /mcL

My melanoma cannot be removed by surgery and has spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Initial administration of EDP1503 for a run-in period

2 weeks

1 visit (in-person)

Treatment

Administration of both EDP1503 (twice daily) and pembrolizumab (every 3 weeks)

Ongoing

Biopsies before treatment and after 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EDP1503
• Pembrolizumab

Trial Overview The study tests if EDP1503 taken orally enhances the effect of pembrolizumab, an immunotherapy drug. Initially, only EDP1503 is given for two weeks; then both drugs are administered together—EDP1503 twice daily and pembrolizumab every three weeks—with required biopsies before and after the run-in period.

How Is the Trial Designed?

Group I: Cohort 2: Anti-PD1 refractory Experimental Treatment 2 Interventions

Participants that have received prior anti-PD1 therapy for their cancer will be enrolled to this arm.

Group II: Cohort 1: Anti-PD1 naive Experimental Treatment 2 Interventions

Participants that have not received prior anti-PD1 therapy for their cancer will be enrolled to this arm.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Evelo Biosciences, Inc.

Industry Sponsor

Trials

11

Recruited

1,500+

Evelo Biosciences

Collaborator

Trials

1

Recruited

8+

Published Research Related to This Trial

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

In a study of 67 advanced melanoma patients treated with pembrolizumab, the drug demonstrated a 27% overall response rate, with 6.5% achieving complete responses, indicating its efficacy even in heavily pretreated patients.

The median overall survival for cutaneous melanoma patients was 14 months, with an 18-month survival rate of 47.1%, and importantly, there were no serious adverse events reported, highlighting the safety of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program. González-Cao, M., Arance, A., Piulats, JM., et al.[2018]

In a randomized trial comparing FDA-approved immune checkpoint inhibitors for advanced melanoma, pembrolizumab showed significantly better treatment outcomes than ipilimumab.

This study is notable as it is the first to directly compare these two therapies as first-line treatments, highlighting pembrolizumab's potential as a more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab superior to ipilimumab in melanoma. [2017]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a real-life study of 125 patients with advanced melanoma treated with pembrolizumab, the median overall survival was 16.9 months, which indicates a significant benefit, but lower than the efficacy seen in clinical trials.

While 82% of patients experienced adverse events, the safety profile was comparable to that observed in the KEYNOTE-006 clinical trial, suggesting that pembrolizumab is generally safe for use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring real-life utilization of pembrolizumab in advanced melanoma using the Portuguese National Cancer Registry. Borges, FC., Ramos, C., Ramos, A., et al.[2021]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03595683?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Evelo%20Biosciences,%20Inc.%22)&viewType=Table&rank=9

Pembrolizumab and EDP1503 in Advanced Melanoma This study is being done to determine if orally administered EDP1503 will enhance the response to standard immunotherapy treatment (pembrolizumab) in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12515240/

Phase 1/2, open-label study of oral bacterial ... Overall, EDP1503 was well tolerated in this population, although the combination of EDP1503 and pembrolizumab demonstrated limited clinical ...

3. merck.com merck.com/news/ten-year-data-for-mercks-keytruda-pembrolizumab-demonstrates-sustained-overall-survival-benefit-versus-ipilimumab-in-advanced-melanoma/

Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

4. aimatmelanoma.org aimatmelanoma.org/io-biotech-announces-phase-3-results-for-cylembio-keytruda-in-advanced-melanoma/

IO Biotech Announces Phase 3 Results for Cylembio® ... “In this study, patients treated with Cylembio in combination with pembrolizumab have achieved the longest median PFS ever observed in a Phase 3 ...

5. keytruda.com keytruda.com/melanoma/advanced/

is an fda-approved treatment for advanced melanoma Clinical Trial Results · KEYTRUDA helped certain people with melanoma live longer compared to another immunotherapy · More people lived longer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04889118

Safety and Efficacy Study of Pembrolizumab (MK-3475 ... The purpose of the China Extension study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7226447/

Public Adverse Event Data Insights into the Safety of ... Additionally, Pembrolizumab was shown to improve OS, response rate and progression-free survival (PFS) compared to Ipilimumab in patients with ...

8. merck.com merck.com/news/merck-and-eisai-provide-update-on-phase-3-trials-of-keytruda-pembrolizumab-plus-lenvima-lenvatinib-in-certain-patients-with-advanced-melanoma-leap-003-and-metastatic-colorectal-cance/

Merck and Eisai Provide Update on Phase 3 Trials of ... The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.