Study of VE800 and Nivolumab in Patients With Selected Types of Advanced or Metastatic Cancer (ConsortiumIO)

Phase 1 Study of VE800 and Nivolumab in Patients With Selected Types of Advanced or Metastatic Cancer

This study evaluated the safety and efficacy of VE800 in combination with nivolumab in patients with selected types of advanced or metastatic cancer

Study Overview

• Status: Completed
• Conditions: Melanoma; Gastric Cancer; Colorectal Cancer; Metastatic Cancer; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Vancomycin Oral Capsule; Biological: VE800

Detailed Description

CONSORTIUM-IO was the first-in-human multicenter, open-label study; the main objectives were to evaluate:

• Safety and tolerability of VE800 in combination with nivolumab
• Efficacy as measured by objective response rate

The study planned to enroll approximately 111 patients with melanoma, gastric/gastroesophageal junction (GEJ) adenocarcinoma, or microsatellite-stable (MSS) colorectal cancer (CRC).

Nivolumab is already approved by the U.S. Food and Drug Administration (FDA), however, it is not approved for the study cancer indications. VE800 was the investigational product, which was designed to enhance the immune response to the tumor.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles
    • Santa Monica, California, United States, 90404
      • The Angeles Clinic and Research Institute - West Los Angeles Office
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Siteman Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10016
      • New York University Medical Oncology Associates
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott and White Center for Advanced Heart and Lung Disese
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute and Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Oncology - First Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Partial Inclusion Criteria:

• Patients with advanced or metastatic cancer who had received no more than 3 lines of prior systemic therapy for advanced/metastatic disease.
• Histologically diagnosed advanced (unresectable) or metastatic cancer with at least one measurable lesion as per RECIST 1.1
• Tumor lesions amenable for biopsy, if deemed safe by the investigator
• Toxicity from prior cancer therapy should have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 (excluding alopecia and neuropathy, where up to Grade 2 residual was allowed)

Partial Exclusion Criteria:

• Prior treatment with immune checkpoint inhibitor (iCPI) (Note: this criterion did not apply to patients with melanoma)
• Receipt of any conventional or investigational systemic anti-cancer therapy within 21 days prior to the first dose of vancomycin
• Concurrent chemotherapy, immunotherapy, biologic, or hormonal anti-cancer therapy. Agents such as bisphosphonates or denosumab were acceptable as prophylaxis for bone metastasis.
• Patients must not have received a transfusion (platelets or red blood cells) within 4 weeks of the first dose of study treatment
• Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment were permitted to enroll.
• Patients with known active hepatitis (e.g., hepatitis B or C) NOTE: Patients with previously treated hepatitis B or C were permitted to enroll if there was evidence of documented resolution of infection.
• Received a fecal transplant, spore or other preparation of fecal material, isolated bacterial products, genetically modified bacteria, or VE800

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VE800 combination treatment with nivolumab; Subjects received 5 days of oral vancomycin, followed by daily VE800 in combination with nivolumab every 4 weeks.

Drug: Nivolumab; Nivolumab is an approved medication that blocks antibodies for certain types of cancer.; Other Names: Opdivo; Drug: Vancomycin Oral Capsule; Vancomycin is an antibiotic used to treat or prevent infection.; Other Names: Vancocin; Biological: VE800; VE800 is an orally administered (PO) live biotherapeutic product (LBP) consisting of 11 distinct nonpathogenic, nontoxigenic, commensal bacterial strains manufactured under Good Manufacturing Practice (GMP) conditions. These strains were selected for their ability to induce an immune response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of VE800 in Combination With Nivolumab: Number of Participants With Adverse Events	Safety and tolerability of VE800 in combination with nivolumab: Number of Participants with Adverse Events	From the first dose to the last dose (up to 56.7 weeks), plus 100 days of post-treatment follow-up
Objective Response Rate (ORR)	Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	18 months (first patient enrolled to last patient visit completed)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Defined as the time from first documentation of complete response (CR) or partial response (PR) until the time of first documentation of progressive disease (PD) according to RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to two years
Best Overall Response	Best response among all overall responses from cycle 1 day 1 (C1D1) until disease progression or start of new anticancer therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 2 years
Disease Control Rate (DCR)	The percentage of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) from cycle 1 day 1 (C1D1) until disease progression (DP) or start of new anticancer therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 2 years
Progression-Free Survival (PFS)	Progression-Free Survival (PFS) is defined as the time from start of treatment to the earlier date of assessment of progression or death by any cause in the absence of progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From the first dose to the last dose (up to 56.7 weeks), plus 100 days of post-treatment follow-up and then follow-up for survival every 90 days.
Overall Survival (OS)	Overall Survival (OS) as measured from the date of start of treatment to the date of death by any cause will also be evaluated.	18 months (first patient enrolled to last patient visit completed)
Detection of VE800 Bacterial Strain Colonization in Stool	Detection of VE800 bacterial strain colonization in stool was measured by pharmacokinetics (PK) of VE800	18 months (first patient enrolled to last patient visit completed)
Degree of VE800 Bacterial Strain Colonization in Stool	Measured by pharmacokinetics (PK) of VE800 colonization in stool	18 months (first patient enrolled to last patient visit completed)
Duration of VE800 Bacterial Strain Colonization in Stool	Measured by pharmacokinetics (PK) of VE800 colonization in stool	18 months (first patient enrolled to last patient visit completed)

Collaborators and Investigators

• Sponsor: Vedanta Biosciences, Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Judy Wang, MD, SCRI - Florida Cancer Specialists - Sarasota Cattlemen Office (Coordinating Investigator)

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): August 26, 2021
• Study Completion (Actual): February 23, 2023

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; Gastric Cancer; Melanoma; Colorectal Cancer; Metastatic Cancer; Opdivo; BMS; Gastroesophageal Junction Adenocarcinoma; Vedanta; VE800; GEJ Adenocarcinoma; CRC-MSS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Esophageal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms; Stomach Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Adenocarcinoma; Melanoma; Esophageal Neoplasms; Neoplasms, Second Primary; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Immune Checkpoint Inhibitors; Vancomycin; Nivolumab
• Other Study ID Numbers: VE800-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No