Clinical Trials /

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

NCT03775850

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Esophagogastric Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of EDP1503 in Patients With Colorectal Cancer, Breast Cancer, and Checkpoint Inhibitor Relapsed Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: EDP1503-101
  • NCT ID: NCT03775850

Conditions

  • Colorectal Cancer Metastatic
  • Triple Negative Breast Cancer
  • Non Small Cell Lung Cancer
  • Bladder Cancer
  • GastroEsophageal Cancer
  • Renal Cell Carcinoma
  • MSI-H

Interventions

DrugSynonymsArms
EDP1503Cohort A
PembrolizumabKeytrudaCohort A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalCohort 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.
  • EDP1503
  • Pembrolizumab
Cohort BExperimentalCohort 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.
  • EDP1503
  • Pembrolizumab
Cohort CExperimentalCohort 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.
  • EDP1503
  • Pembrolizumab

Eligibility Criteria

        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 archival tumor tissue sample 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of EDP1503 alone and in combination with pembrolizumab as assessed per CTCAE v5.0
Time Frame:2 years
Safety Issue:
Description:Number of participants with EPD1503 related adverse events as assessed per CTCAE v5.0

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:Progression Free Survival
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Evelo Biosciences, Inc.

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