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

Colorectal Cancer Clinical Trial

— ConsortiumIO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04208958
• Other study ID #: VE800-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 23, 2020
• Est. completion date: February 23, 2023

Study information

• Verified date: March 2023
• Source: Vedanta Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: February 23, 2023
• Est. primary completion date: August 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Esophageal Neoplasms
• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Melanoma
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary
• Stomach Neoplasms

Intervention

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.

Drug:
• Nivolumab
Nivolumab is an approved medication that blocks antibodies for certain types of cancer.
• Vancomycin Oral Capsule
Vancomycin is an antibiotic used to treat or prevent infection.

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois
United States	Baylor Scott and White Center for Advanced Heart and Lung Disese	Dallas	Texas
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of California Los Angeles	Los Angeles	California
United States	New York University Medical Oncology Associates	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	The Miriam Hospital	Providence	Rhode Island
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute and Hospital	Salt Lake City	Utah
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	The Angeles Clinic and Research Institute - West Los Angeles Office	Santa Monica	California
United States	University of California Los Angeles	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	HonorHealth Research Institute	Scottsdale	Arizona
United States	Swedish Medical Oncology - First Hill	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Vedanta Biosciences, Inc.	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)