A Phase 1 Open Label Trial of Intravenous Administration of MVA-BN-Brachyury Vaccine in Patients With Advanced Cancer

NCT04134312 | Completed Phase 1 FDA Drug

• 1 other identifier: MVA-BN-BRACHY-IV-001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1 open label trial of intravenous administration of MVA-BN-Brachyury vaccine in patients with advanced cancer. Patients with metastatic or unresectable locally advanced malignant solid tumors will be enrolled and treated according to a 3+3 dose escalation scheme. Up to 3 dose levels will be explored. Patients will receive MVA-BN-Brachyury every three weeks, three administrations in total. Patients will be hospitalized after each vaccination, over 48 hours. Trial duration will be approximately 24 weeks per patient including 3 months after the last vaccination follow up (FU) period.

Conditions

Solid Metastatic Tumor

Outcome Measures

Primary Outcomes (1)

• Patients with Dose Limiting Toxicity (DLT)

  Frequency of patients with DLTs

  DLT assessment is done 7 days after 2nd vaccination of last patient in each dose level

Study Arms (1)

MVA-BN-Brachyury IV

EXPERIMENTAL

MVA-BN-Brachyury will be administered intravenously every three weeks with three administrations in total at the dose indicated by the enrolled cohort.

Biological: MVA-BN-Brachyury

Interventions

MVA-BN-Brachyury BIOLOGICAL

MVA-BN-Brachyury will be administered intravenously every three weeks with three administrations in total at the dose indicated by the enrolled cohort.

MVA-BN-Brachyury IV

Eligibility Criteria

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

You may qualify if:

• Men and women \> 18 years old.
• Patients must be able to understand and be willing to sign a written informed consent document.
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Eligible patients must have one of the histologically confirmed cancers and treatment history as described:
• Chordoma
• Symptomatic, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease.
• Only curative interventions are required as prior therapy (surgery or definitive radiation) as no known systemic therapies have proven benefit.
• Non-Small Cell Lung Cancer
• Metastatic or incurable locally advanced.
• Disease progression after indicated targeted therapy (EGFR-mut, ALK-fusion, BRAF-mut).
• Disease progression after one regimen of chemotherapy and anti-PD-1/L1 therapy either sequentially or concurrently.
• Small Cell Lung Cancer
• Metastatic disease.
• Disease progression after 1st line chemotherapy.
• Breast

You may not qualify if:

• Receipt of an investigational agent within 28 days of the first planned dose of MVA-BN-Brachyury vaccine.
• Known metastatic disease to the central nervous system, unless previously treated and well controlled for at least 3 months (clinically stable, no edema, no steroid treatment required).
• History of anaphylaxis or severe allergic reaction to any vaccine, aminoglycoside antibiotics or egg products.
• Active infection within 72 hours prior to vaccination.
• Administration of antibiotics within 7 days prior to initial vaccination.
• Subjects having known evidence of being immunocompromised as listed below:
• Human immunodeficiency virus (HIV) positivity, active chronic hepatitis infection, including B and C.
• Active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, and psoriasis not requiring systemic treatment are permitted.
• Immunosuppressive therapy for post-organ transplant.
• Chronic administration (defined as \> 5 consecutive days of \> 15 mg of prednisone (or equivalent) per day) of systemic corticosteroids within 14 days of the first planned dose of MVA-BN-Brachyury vaccine. Use of inhaled steroids, nasal sprays, eye drops, and topical creams is allowed. Steroids premedication for CT scans is allowed.
• Vaccinations or planned vaccinations with a live vaccine within 30 days prior to the trial vaccination or with an inactivated vaccine within 14 days prior to the trial vaccination.
• Patients with history of myocardial infarction, unstable angina pectoris, history of or existing CHF (NYHA Class II -IV), other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion.
• Known history of, or any evidence of active, non-infectious pneumonitis or primary pulmonary fibrosis.
• Psychiatric illness/social situations that, in the opinion of the Investigator, would limit compliance with trial requirements.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Bavarian Nordic: lead

Study Sites (1)

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• DeMaria PJ, Lee-Wisdom K, Donahue RN, Madan RA, Karzai F, Schwab A, Palena C, Jochems C, Floudas C, Strauss J, Marte JL, Redman JM, Dombi E, Widemann B, Korchin B, Adams T, Pico-Navarro C, Heery C, Schlom J, Gulley JL, Bilusic M. Phase 1 open-label trial of intravenous administration of MVA-BN-brachyury-TRICOM vaccine in patients with advanced cancer. J Immunother Cancer. 2021 Sep;9(9):e003238. doi: 10.1136/jitc-2021-003238.

  PMID: 34479925 DERIVED

• Wedekind MF, Widemann BC, Cote G. Chordoma: Current status, problems, and future directions. Curr Probl Cancer. 2021 Aug;45(4):100771. doi: 10.1016/j.currproblcancer.2021.100771. Epub 2021 Jul 1.

  PMID: 34266694 DERIVED

Study Officials

• Marijo Bilusic, MD,PhD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 22, 2019
• Study Start: January 8, 2020
• Primary Completion: January 12, 2021
• Study Completion: April 6, 2021
• Last Updated: July 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)