Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (MCGRAW)

June 7, 2022 updated by: Parker Institute for Cancer Immunotherapy

A Multicenter Phase 1b Randomized, Placebo-controlled, Blinded Study to Evaluate the Safety, Tolerability and Efficacy of Microbiome Study Intervention Administration in Combination With Anti-PD-1 Therapy in Adult Patients With Unresectable or Metastatic Melanoma

This study is designed to evaluate the safety and tolerability of treatment with oral microbiome study intervention (SER-401) or matching placebo in combination with anti-programmed cell death 1 (anti-PD-1) therapy (nivolumab) in participants with unresectable or metastatic melanoma. The study also intends to assess clinical outcomes, the impact of microbiome study intervention administration on the microbiome profile, and its association with clinical and immunological outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1b, multicenter, randomized, placebo-controlled, blinded study in adult participants with anti-PD-1 therapy naïve, unresectable or metastatic melanoma to evaluate the safety and tolerability of SER-401, or matching placebo in combination with anti-PD-1 therapy (nivolumab). Prior to initiating microbiome study intervention and nivolumab, participants will undergo an antibiotic or antibiotic placebo treatment lead-in to prime the gut microbiome for engraftment of the oral microbiome study intervention. Study intervention groups will be assessed for safety, changes in the microbiome, changes in the percentage of tumoral CD8 T cells, and antitumor activity. Participants must have measurable disease that can be biopsied and consent to baseline and on-treatment biopsies, as well as stool and blood biomarker collection throughout the study.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90025
        • The Angeles Clinic and Research Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Participant must be willing to provide a baseline stool sample.
  2. Histologically-confirmed Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Participants with a history of uveal melanoma are not eligible.

  3. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1; ie, defined as at least 1 lesion that can be accurately measured in at least 1 dimension [longest diameter to be recorded] with a minimum size of ≥ 10 mm by computerized tomography [CT] scan or caliper measurement on clinical exam or ≥ 20 mm by chest X-ray).

    1. Malignant lymph nodes must be ≥ 15 mm in short axis when assessed by CT scan to be considered pathologically enlarged and measurable.
    2. Participants must have at least one measurable lesion by RECIST and a separate lesion amenable to biopsy that has not been previously irradiated.

    i. Participants must be willing to undergo a newly-obtained core needle or incisional biopsy at baseline (prior to antibiotic or antibiotic placebo administration). Fine needle aspiration is not acceptable.

  4. Participants must be willing to undergo tumor biopsy on treatment.

  5. Prior adjuvant or neoadjuvant melanoma therapy is permitted if completed at least 6 weeks prior to randomization and all related AEs have either returned to baseline or stabilized.

    1. Prior anti-CTLA-4 therapy in the adjuvant setting is allowed if completed at least 12 weeks prior to the first dose of anti-PD-1.

Exclusion Criteria:

  1. Participants who require hemodialysis.
  2. Participants with a history of another cancer in the last 5 years, except for: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systemic therapy; and c) other primary tumors with no known active disease present that, in the opinion of the Investigator and the Sponsor, will not affect participant outcome in the setting of the current diagnosis.

  3. Any known, untreated brain metastases. Participants with brain metastases are eligible if these have been treated, and provided:

    1. Brain metastases must be stable (image-documented) 4 weeks after completion of treatment for brain metastases and require treatment with less than 10 mg/day prednisone equivalent for at least 2 weeks prior to study intervention administration.
    2. Neurological symptoms should be absent or returned to baseline.

  4. Prior checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 in the adjuvant setting.

    a. Exception: Participants with stage 3 or 4 cutaneous melanoma status post-resection who have received up to one year of adjuvant anti-PD-1 therapy who have recurred > 6 months after their last dose of anti-PD-1 therapy are eligible.

  5. Other prior systemic treatment (ie, anticancer chemotherapy, immunotherapy, or investigational agents) for unresectable or metastatic melanoma EXCEPT:

    1. Prior BRAF-targeted therapy (ie, BRAF or BRAF-MEK) in the metastatic setting is allowed if completed at least 4 weeks prior to the first dose of anti-PD-1.
    2. Prior anti-CTLA 4 therapy in the adjuvant setting are allowed if completed at least 12 weeks prior to the first dose of anti-PD-1.
  6. History of active inflammatory bowel disease (eg, active Crohn's disease or ulcerative colitis) with diarrhea OR major gastrointestinal surgery (not including appendectomy or cholecystectomy) within 3 months of enrollment (ie, signed informed consent for the study), OR any history of total colectomy or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, ie, restrictive procedures such as banding, are permitted).

  7. Any diagnosis of autoimmune disease. Participants with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, adrenal insufficiency on replacement dose steroids, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

    a. Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.

  8. Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study intervention administration or has a contrast allergy requiring premedication with corticosteroids. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

  9. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (ie, bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.

    a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

  10. Has a transplanted organ or has undergone allogeneic bone marrow transplant.
  11. Has received a live vaccine within 30 days prior to first dose. Participants must not receive live, attended influenza vaccine (eg, FluMist) within 30 days prior to Cycle 1, Day 1 or at any time during the study and 100 days after last dose of nivolumab.
  12. Has used antibiotics within 30 days prior to randomization or has planned or required need for antibiotic prophylaxis for more than 24 consecutive hours during the course of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: SER-401 Matching Placebo/ Nivolumab
Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment.
Drug: Placebo for antibiotic
Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout.
Drug: Nivolumab
Nivolumab (480 mg) will be administered intravenously (IV) according to institutional guidelines every 4 weeks for up to 12 cycles. A cycle is defined as 4 calendar weeks.
Other Names:
  • Opdivo
Drug: Matching Placebo for SER-401
Administered once a day for 7 days during the lead-in phase, followed by once a day for 8 weeks during the microbiome/anti-PD-1 treatment phase.
Experimental: SER-401/ Nivolumab
Participants will undergo a 4-day lead-in pretreatment with antibiotic (vancomycin) to prime the gut microbiome for engraftment of the oral microbiome study intervention, then SER-401 and nivolumab treatment.
Drug: Nivolumab
Nivolumab (480 mg) will be administered intravenously (IV) according to institutional guidelines every 4 weeks for up to 12 cycles. A cycle is defined as 4 calendar weeks.
Other Names:
  • Opdivo
Drug: Vancomycin pretreatment
Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout.
Drug: SER-401
Administered once a day for 7 days during the lead-in phase, followed by once a day for 8 weeks during the microbiome/anti-PD-1 treatment phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients with Adverse Events (AEs)
Time Frame: Up to 2 years
Up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the engraftment of SER-401 bacteria in microbiome study intervention group relative to placebo.
Time Frame: Up to 2 years
Up to 2 years
Objective response rate (ORR) at Weeks 24 and 52
Time Frame: Up to week 52
Defined as complete response (CR) or partial response (PR) as best response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 assessment.
Up to week 52
Disease control rate (DCR) at Weeks 24 and 52
Time Frame: Up to week 52
Defined as CR, PR, or stable disease (SD) for ≥ 24 weeks as best response by RECIST v1.1.
Up to week 52
Progression-free survival (PFS) Progression free survival
Time Frame: Up to 2 years
Defined as the time from randomization to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented progression-free status
Up to 2 years
Overall survival [OS]
Time Frame: Up to 2 years
Defined as the time from randomization until death or last contact if still alive at the time of final data collection (after completion of anti-PD-1 therapy).
Up to 2 years
Duration of response
Time Frame: Up to 2 years
Defined as time from date of documented CR or PR to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented response (ie, scan date).
Up to 2 years
Change in the percentage of CD8 cells in tumor tissue from baseline at Cycle 2.
Time Frame: At cycle 2 (each cycle is 28 days)
At cycle 2 (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Parker Institute for Cancer Immunotherapy

Collaborators

Seres Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2019

Primary Completion (Actual)

March 4, 2022

Study Completion (Actual)

March 4, 2022

Study Registration Dates

First Submitted

January 18, 2019

First Submitted That Met QC Criteria

January 22, 2019

First Posted (Actual)

January 25, 2019

Study Record Updates

Last Update Posted (Actual)

June 9, 2022

Last Update Submitted That Met QC Criteria

June 7, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PICI0014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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