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

Phase 1
Completed
Conditions
Metastatic Cancer
Melanoma
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Colorectal Cancer
Interventions
Registration Number
NCT04208958
Lead Sponsor
Vedanta Biosciences, Inc.
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
VE800 combination treatment with nivolumabVE800Subjects received 5 days of oral vancomycin, followed by daily VE800 in combination with nivolumab every 4 weeks.
VE800 combination treatment with nivolumabNivolumabSubjects received 5 days of oral vancomycin, followed by daily VE800 in combination with nivolumab every 4 weeks.
VE800 combination treatment with nivolumabVancomycin Oral CapsuleSubjects received 5 days of oral vancomycin, followed by daily VE800 in combination with nivolumab every 4 weeks.
Primary Outcome Measures
NameTimeMethod
Safety and Tolerability of VE800 in Combination With Nivolumab: Number of Participants With Adverse EventsFrom the first dose to the last dose (up to 56.7 weeks), plus 100 days of post-treatment follow-up

Safety and tolerability of VE800 in combination with nivolumab: Number of Participants with Adverse Events

Objective Response Rate (ORR)18 months (first patient enrolled to last patient visit completed)

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.

Secondary Outcome Measures
NameTimeMethod
Duration of Response (DOR)Up to two years

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.

Overall Survival (OS)18 months (first patient enrolled to last patient visit completed)

Overall Survival (OS) as measured from the date of start of treatment to the date of death by any cause will also be evaluated.

Detection of VE800 Bacterial Strain Colonization in Stool18 months (first patient enrolled to last patient visit completed)

Detection of VE800 bacterial strain colonization in stool was measured by pharmacokinetics (PK) of VE800

Degree of VE800 Bacterial Strain Colonization in Stool18 months (first patient enrolled to last patient visit completed)

Measured by pharmacokinetics (PK) of VE800 colonization in stool

Duration of VE800 Bacterial Strain Colonization in Stool18 months (first patient enrolled to last patient visit completed)

Measured by pharmacokinetics (PK) of VE800 colonization in stool

Best Overall ResponseUp to 2 years

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.

Disease Control Rate (DCR)Up to 2 years

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.

Progression-Free Survival (PFS)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.

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

Trial Locations

Locations (17)

University of California Los Angeles

🇺🇸

Santa Monica, California, United States

Baylor Scott and White Center for Advanced Heart and Lung Disese

🇺🇸

Dallas, Texas, United States

Florida Cancer Specialists

🇺🇸

Sarasota, Florida, United States

Indiana University Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Swedish Medical Oncology - First Hill

🇺🇸

Seattle, Washington, United States

New York University Medical Oncology Associates

🇺🇸

New York, New York, United States

The Angeles Clinic and Research Institute - West Los Angeles Office

🇺🇸

Santa Monica, California, United States

UPMC Hillman Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

HonorHealth Research Institute

🇺🇸

Scottsdale, Arizona, United States

Weill Cornell Medicine

🇺🇸

New York, New York, United States

John Theurer Cancer Center

🇺🇸

Hackensack, New Jersey, United States

The University of Chicago

🇺🇸

Chicago, Illinois, United States

The Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

Huntsman Cancer Institute and Hospital

🇺🇸

Salt Lake City, Utah, United States

Washington University School of Medicine Siteman Cancer Center

🇺🇸

Saint Louis, Missouri, United States

Pacific Hematology Oncology Associates

🇺🇸

San Francisco, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

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