Pembrolizumab and EDP1503 in Advanced Melanoma

NCT03595683 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: IRB17-0461
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to determine if orally administered EDP1503 will enhance the response to standard immunotherapy treatment (pembrolizumab) in participants with advanced melanoma. The study will involve initial administration of EDP1503 for a run-in period (2 weeks) followed by administration of both EDP1503 (twice daily) and pembrolizumab (every 3 weeks). Mandatory biopsies are required before starting study treatment and after 2 weeks of EDP1503 dosing.

Conditions

Melanoma (Skin); Melanoma

Outcome Measures

Primary Outcomes (2)

• Response Rate

  For Cohort 1, based on deep response (\>80% tumor reduction). Assessed by standard RECIST criteria for Cohort 2 (complete + partial response).

  2 years

• Number of Participants With EPD1503 Related Adverse Events During the Run in Period

  Assessed by CTCAE v4.0, grade 3 or higher

  2 weeks

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  2 years

• Number of Participants With Treatment Related Adverse Events During Combination Therapy

  2 years

Study Arms (2)

Cohort 1: Anti-PD1 naive

EXPERIMENTAL

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

Drug: Pembrolizumab; Biological: EDP1503

Cohort 2: Anti-PD1 refractory

EXPERIMENTAL

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

Drug: Pembrolizumab; Biological: EDP1503

Interventions

Pembrolizumab DRUG

200 mg given by intravenous (IV) infusion once every 3 weeks.

Also known as: Keytruda

Cohort 1: Anti-PD1 naive; Cohort 2: Anti-PD1 refractory

EDP1503 BIOLOGICAL

Taken by mouth twice daily. Each capsule will contain ≥ 7.5x10\^10 colony-forming units (CFU).

Cohort 1: Anti-PD1 naive; Cohort 2: Anti-PD1 refractory

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced, unresectable or metastatic melanoma
• Be willing and able to provide written informed consent/assent for the trial.
• Aged 18 years or older on day of signing informed consent.
• Have measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
• Be naïve to exposure in the metastatic setting to PD1/L1 antibody for cohort 1 but have had exposure to PD1/L1 (or PD1/L1 combination therapy) in cohort 2. Prior exposure to CTLA4 antibody in the metastatic setting is not allowed for cohort 1 though exposure in the adjuvant setting is allowed for either cohort. To be eligible for cohort 2, and considered refractory to PD1/L1, a patient must have had a restaging exam showing progressive disease at least 90 days following initiation of anti-PD1/L1 as prior therapy.
• Adjuvant therapy with BRAF-MEK, PD1 or CTLA4 based therapy is allowed. Prior adjuvant BRAF-MEK therapy will fulfill treatment requirement in the metastatic setting. Patients who experience progression of disease during adjuvant PD1 therapy or within 6 months of completing adjuvant PD1 therapy will be considered refractory and thus eligible for cohort 1. Patients with progression to active metastatic disease more than 6 months following completion of adjuvant PD1 therapy will be eligible for cohort 1.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of study initiation.
• Adequate Organ Function Laboratory Values
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

You may not qualify if:

• For cohort 2: Has BRAF mutant disease but has not yet received treatment with RAF/MEK inhibitors. This criteria can be met via adjuvant treatment with BRAF-MEK inhibitors
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks of the first dose.
• Is currently taking Bifidobacterium based probiotics or is taking pre/pro-biotics regularly.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study Day 1 (excluding anti-PD1 antibodies such as pembrolizumab or nivolumab in cohort 2) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to start of study. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring antibiotic therapy or has received a course of antibiotics within the previous 2 weeks of starting study treatment.

Sponsors & Collaborators

• University of Chicago: lead
• Merck Sharp & Dohme LLC: collaborator
• Evelo Biosciences, Inc.: collaborator

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Randy Sweis
• Organization: University of Chicago

rsweis@uchicago.edu

773-834-3094

Study Officials

• Jason Luke, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: July 23, 2018
• Study Start: October 2, 2018
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: December 8, 2025
• Results First Posted: December 8, 2025

Record last verified: 2025-12

Locations

US (1)