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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Metastatic Cancer, Melanoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Colorectal Cancer

Intervention / Treatment
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* Biological: VE800
* Drug: Nivolumab
* Drug: Vancomycin Oral Capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study was designed to help determine the safety and effectiveness of the study drug, VE800, in combination with nivolumab in patients with advanced/metastatic cancer. The following cohorts of patients with advanced/metastatic cancer were enrolled: Melanoma Gastric/gastroesophageal junction (GEJ) adenocarcinoma Colorectal cancer (microsatellite-stable) (CRC-MSS)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VE800 combination treatment with nivolumab<br>Subjects received 5 days of oral vancomycin, followed by daily VE800 in combination with nivolumab every 4 weeks. | Biological: VE800<br>* 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.<br>Drug: Nivolumab<br>* Nivolumab is an approved medication that blocks antibodies for certain types of cancer.<br>* Other names: Opdivo;Drug: Vancomycin Oral Capsule<br>* Vancomycin is an antibiotic used to treat or prevent infection.<br>* Other names: Vancocin;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GEJ Adenocarcinoma, Metastatic Cancer, VE800, Nivolumab, Opdivo, Melanoma, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Colorectal Cancer, CRC-MSS, Vedanta, BMS