VB-111 in Combination With Nivolumab in People With Metastatic Colorectal Cancer (mCRC)

NCT04166383 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20002220-C-0022
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Gastrointestinal cancer is one of the most common cancers worldwide. Researchers think an unmet need exists to understand and improve treatment options. They want to see if a combination of drugs can help people with metastatic colorectal cancer. Objective: To see if using a combination of Vascular Biogenics (VB)-111 and nivolumab is safe and will cause colorectal tumors to shrink. Eligibility: People ages 18 and older with microsatellite stable colorectal cancer that has spread to the liver Design: Participants must consent to sample collection protocol 11C0112. Participants will be screened with: Blood tests Scans Tumor samples. If these are not available, participants will have a biopsy. Before they start treatment and with every treatment cycle, participants will have: Physical exams Blood tests Heart tests Before they start treatment and every 4 cycles, participants will have computed tomography (CT) or magnetic resonance imaging (MRI) scans. For these, they will lie in a machine that takes pictures of the body. For the MRI, a soft padding or coil will be placed around their head. Participants will have biopsies before they start therapy. They will have them again after 2 6 weeks on study. On day 1 of 14-day cycles, participants will get one or both study drugs by vein. After they finish treatment, participants will have monthly visits for 3 months. They will have a physical exam and blood tests. If participants stop treatment for reasons other than their disease getting worse, they will have scans about every 8 weeks. This will continue until their disease gets worse. Participants will be contacted by phone or email every 6 months. This will continue for life. ...

Conditions

Metastatic Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Cancer With Hepatic Metastases; Colorectal Tumors

Keywords

Nonreplicating adenovirus; Antitumor Immunity; PD-1 inhibition; Immune Checkpoint Inhibition

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Grade 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events That Are Possibly, Probably and/or Definitely Related to Drug

  Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v5.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

  90 days after treatment

• Best Overall Response (BOR)

  Best overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

  Follow up visits are planned to be performed at 60 (+/- 14 days) and 90 (+/- 14 days) days after treatment discontinuation to evaluate patient's safety, up to 6 months.

Secondary Outcomes (3)

• Median Progression-free Survival (PFS)

  The time between the first day of treatment to the day of disease progression, an average of 1.8 months.

• Median Overall Survival (OS)

  The time between the first day of treatment to the day of death, an average of 6.9 months.

• 6-month Progression-free Survival (PFS)

  6 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, an average of 28 months and 23 days.

Study Arms (1)

1/Arm 1

EXPERIMENTAL

Vascular Biogenics (VB)-111 and nivolumab

Biological: Vascular Biogenics (VB)-111; Drug: Nivolumab

Interventions

Vascular Biogenics (VB)-111 BIOLOGICAL

1E13 or 0.7E13 VP via intravenous (IV) infusion on Day 1 of cycle 1 and continue every 6 weeks

1/Arm 1

Nivolumab DRUG

240 mg of nivolumab via intravenous (IV) infusion on Day 1 of each cycle starting on cycle 2 and continue every 2 weeks

Also known as: Opdivo

1/Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological confirmation of colorectal cancer.
• Patients must have radiologically confirmed liver metastasis.
• Patients must:
• have progressed on \> 2 lines of standard of care chemotherapy for colorectal cancer
• been intolerant of standard of care chemotherapy for colorectal cancer
• refused prior standard of care chemotherapy for colorectal cancer.
• Patients who have a known Kirsten rat sarcoma (KRAS) wild type tumor must have progressed, been intolerant of or refused anti-epidermal growth factor receptor (EGFR) based treatment.
• Patient's tumors must be documented to be microsatellite stable (MSS).
• Patients must have at least 1 focus of metastatic disease that is amenable to pre- and on-treatment biopsies and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigator's
• Patients must have measurable disease by RECIST v 1.1 criteria.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of nivolumab in combination with Vascular Biogenics (VB)-111 in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate hematological function defined by:
• white blood cell (WBC) count greater than or equal to 3x10(9)/L
• absolute neutrophil count (ANC) greater than or equal to 1.5x10(9)/L

You may not qualify if:

• Patients who have had standard-of-care anti-cancer therapy or therapy with investigational agents (e.g., chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies or other investigation agents), large field radiotherapy, or major surgery within 4 weeks prior to enrollment.
• Patients who have had anti-vascular endothelial growth factor (VEGF) therapy within 4 weeks prior to enrollment.
• Patients currently on a corticosteroid dose greater than physiologic replacement dosing defined as 10 mg of cortisone per day or its equivalent.
• Patients with known brain metastases because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with signs of liver failure, e.g., clinically significant ascites, encephalopathy, or variceal bleeding within 6 months prior to enrollment.
• Prior major liver resection: remnant liver \<50% of the initial liver volume. Patients with a biliary stent can be included.
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.
• Of note, patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (within timeframes identified in the bullets below) that would limit compliance with study requirements.
• History of severe or unstable cerebrovascular disease.
• Pulse oximetry \< 92% on room air
• Myocardial infarction within 6 months prior to enrollment
• History of myocarditis
• Sustained hypotension (\<90/50 mmHg) or uncontrolled hypertension (\>160/100 mmHg)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Coffman-D'Annibale K, Myojin Y, Monge C, Xie C, Hrones DM, Wood BJ, Levy EB, Kleiner D, Figg WD, Steinberg SM, Redd B, Greten TF. VB-111 (ofranergene obadenovec) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single center, single arm, phase II trial. J Immunother Cancer. 2024 Jan 6;12(1):e008079. doi: 10.1136/jitc-2023-008079.

  PMID: 38184304 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Tim F. Greten
• Organization: National Cancer Institute

gretentf@mail.nih.gov

240-760-6114

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 18, 2019
• Study Start: August 9, 2020
• Primary Completion: April 12, 2022
• Study Completion: December 31, 2022
• Last Updated: March 10, 2026
• Results First Posted: June 9, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)