Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of EDP1503 in Patients With Colorectal Cancer, Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03775850
Recruitment Status : Recruiting
First Posted : December 14, 2018
Last Update Posted : July 14, 2020
Sponsor:
Collaborators:
SCRI Development Innovations, LLC
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Evelo Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE December 12, 2018
First Posted Date  ICMJE December 14, 2018
Last Update Posted Date July 14, 2020
Actual Study Start Date  ICMJE December 19, 2018
Estimated Primary Completion Date December 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 12, 2018)
  • Safety and tolerability of EDP1503 alone and in combination with pembrolizumab as assessed per CTCAE v5.0 [ Time Frame: 2 years ]
    Number of participants with EPD1503 related adverse events as assessed per CTCAE v5.0
  • Safety and tolerability of EDP1503 alone and in combination with pembrolizumab [ Time Frame: 2 years ]
    Safety and tolerability of EDP1503 alone and in combination with pembrolizumab assessed via clinical laboratory evaluations
  • Evidence of anti-tumor activity of EDP1503 based on ORR [ Time Frame: 2 years ]
    To determine preliminary evidence of anti-tumor activity of EDP1503 in patients
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2018)
  • Progression Free Survival [ Time Frame: 2 years ]
    Progression Free Survival
  • Overall Survival [ Time Frame: 2 years ]
    Overall Survival
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of EDP1503 in Patients With Colorectal Cancer, Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors
Official Title  ICMJE A Phase I/II Open-label Study of EDP1503 Alone and in Combination With Pembrolizumab in Patients With Advanced Metastatic Colorectal Carcinoma, Triple-negative Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors
Brief Summary This study is being conducted to assess the safety, tolerability, and efficacy of EDP1503 alone and in combination with pembrolizumab in patients with advanced metastatic colorectal carcinoma, triple-negative breast cancer, and checkpoint inhibitor relapsed tumors
Detailed Description This will be a Phase I/II open-label study which will involve a 2-week monotherapy with EDP1503, following which the patients will be dosed with a combination of EDP1503 and pembrolizumab.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will be assigned to one of three cohorts based on disease condition: Cohort A (microsatellite stable colorectal cancer); Cohort B (Triple negative breast cancer); Cohort C (PD-1 relapsed tumors: non small cell lung cancer, gastroesophageal cancer, or any microsatellite unstable or renal cell carcinoma). Patients will receive monotherapy with EDP1503 for a period of 2 weeks, following which they will be dosed with a combination of EDP1503 and pembrolizumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer Metastatic
  • Triple Negative Breast Cancer
  • Non Small Cell Lung Cancer
  • Bladder Cancer
  • GastroEsophageal Cancer
  • Renal Cell Carcinoma
  • MSI-H
Intervention  ICMJE
  • Biological: EDP1503
    4 capsules taken by mouth twice daily. Each capsule will contain ≥ 7.5x10^10 colony-forming units (CFU)
  • Biological: Pembrolizumab
    200 mg given by intravenous (IV) infusion once every 3 weeks
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Cohort A
    Cohort A includes patients with microsatellite stable (MSS) colorectal cancer (CRC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
    Interventions:
    • Biological: EDP1503
    • Biological: Pembrolizumab
  • Experimental: Cohort B
    Cohort B includes patients with Triple Negative Breast Cancer (TNBC). Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
    Interventions:
    • Biological: EDP1503
    • Biological: Pembrolizumab
  • Experimental: Cohort C
    Cohort C includes patients with non-small-cell lung cancer (NSCLC), bladder cancer; gastroesophageal (GE) cancer, any microsatellite unstable, or renal cell carcinoma (RCC) who are relapsed to prior PD-1/L1 therapy. Patients will receive a 14 day run-in of EDP1503 alone, following which they will be treated with a combination of EDP1503 and pembrolizumab.
    Interventions:
    • Biological: EDP1503
    • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 12, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 19, 2020
Estimated Primary Completion Date December 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Selected Inclusion Criteria:

  1. Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors who have had disease progression after treatment with all available therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
  2. Have adequate organ function as defined in the clinical protocol. Specimens must be collected within 10 days prior to the start of study treatment.
  3. Have provided an archival tumor tissue sample obtained since the most recent prior anticancer regimen or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
  4. Measurable disease by RECIST v1.1 as assessed by the local site investigator/radiologist. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. Metastatic disease not suitable for upfront curative-intent surgery.
  6. Progressive disease on previous line of therapy per treating investigator (additional specific criteria for cohort C).
  7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  8. Additional tumor-specific inclusion criteria

Selected Exclusion Criteria:

  1. Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  2. Treatment with investigational therapy within 28 days prior to initiation of study treatment.
  3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
  4. Has received prior systemic anti-cancer therapy within 28 days or 5 half-lives, whichever is shorter prior to treatment.

    Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible.

    Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

  5. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    1. Unstable angina or acute myocardial infarction ≤ 3 months prior to C1D1;
    2. Clinically significant heart disease (e.g., symptomatic congestive heart failure [e.g., >NYHA Class 2]; uncontrolled arrhythmia, or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen).
  6. Uncontrolled active severe systemic infection requiring parenteral antibiotics within 1 week, and systemic antivirals or antifungals within two weeks prior to C1D1.
  7. Patients with active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  8. Patients with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  9. Prior malignancies:

    1. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (i.e. cervix, breast) may enroll irrespective of the time of diagnosis.
    2. Patients with a known additional malignancy that is progressing or has required active treatment within the past which may interfere with the interpretation of the study. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Sponsor. Cancer treated with curative intent > 5 years previously and without evidence of recurrence will be allowed.
  10. Patients with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  11. Patients with uncontrolled vomiting or dirrahea that could interfere with the GI exposure to EDP1503.
  12. Patients who are transfusion dependent should be discussed with the Medical Monitor
  13. Patients unwilling to comply with the protocol including required biopsies and sample collections required to measure disease.
  14. 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 (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  15. Has received a live vaccine within 30 days of planned C1D1. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed. Intranasal influenza vaccines (e.g FluMist) are live attenuated vaccines and are not allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sarah Cannon Development Innovations, LLC 844-710-6157 CANN.InnovationsMedical@sarahcannon.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03775850
Other Study ID Numbers  ICMJE EDP1503-101
KEYNOTE-939 ( Other Identifier: Merck Sharp & Dohme Corp. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Evelo Biosciences, Inc.
Study Sponsor  ICMJE Evelo Biosciences, Inc.
Collaborators  ICMJE
  • SCRI Development Innovations, LLC
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Johanna Bendell, MD SCRI Development Innovations, LLC
PRS Account Evelo Biosciences, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP