First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector

NCT04053283 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: NG-641-01
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 6

Brief Summary

To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.

Conditions

Metastatic Cancer; Epithelial Tumor

Keywords

metastatic; epithelial; virus; advanced; PsiOxus

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (safety and tolerability) in study NG-641

  Incidence of adverse events, adverse events meeting protocol-defined DLT criteria, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death.

  End of study treatment visit

Study Arms (1)

Intravenous

EXPERIMENTAL

Phase 1a dose escalation: one cycle of treatment. Phase 1a dose optimisation: up to 8 cycles of treatment

Biological: NG-641

Interventions

NG-641 BIOLOGICAL

NG-641 is a replication competent adenoviral vector producing a bispecific T cell activator (TAc) targeting fibroblast activation protein (FAP) plus immune enhancer genes CXCL9/CXCL10/IFNa2. This can lead to killing of tumor cells and stimulation of immunity against the tumor cells.

Intravenous

Eligibility Criteria

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

You may qualify if:

• Phase 1a:
• \- Histologically or cytologically documented metastatic or advanced epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available
• All patients
• Provide written informed consent to participate
• At least one measurable site of disease according to RECIST Version 1.1 criteria
• Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
• Ability to comply with study procedures in the Investigator's opinion
• Aged 18 years or over
• ECOG performance status 0 or 1
• Predicted life expectancy of 6 months or more
• Adequate lung reserve
• Adequate renal function
• Adequate hepatic function
• Adequate bone marrow function
• Meeting reproductive status requirements

You may not qualify if:

• Prior or planned allogenic or autologous bone marrow or organ transplantation
• Splenectomy
• Active infections requiring antibiotics, physician monitoring or systemic therapy within 1 week of the anticipated first dose of study drug, or recurrent fevers (\>38.0˚C) associated with a clinical diagnosis of active infection
• Treatment with the antiviral agents: ribavirin, adefovir, lamivudine, cidofovir or paxlovid within 10 days prior to the first dose of study treatment; or pegylated interferon in the 4 weeks before the first dose of study treatment
• Known history of hepatitis B infection or known active hepatitis C infection. Known history of HIV infection
• Patients who have active, known or suspected autoimmune disease that has required systemic therapy in the past 2 years, are immunocompromised in the opinion of the Investigator, or are receiving systemic immunosuppressive treatment
• Treatment with any live, live-attenuated or COVID-19 vaccine in the 28 days before the first dose of NG-641
• Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before the first dose of NG-641
• History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
• History of clinically significant interstitial lung disease or non-infectious pneumonitis
• Lymphangitic carcinomatosis
• Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
• Any known CTCAE Grade ≥2 coagulation abnormality/coagulopathy
• Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or thromboembolic event in the 6 months before the first dose of study treatment
• Grade 3 or 4 gastrointestinal bleeding All toxicities attributed to prior anti-cancer therapy (including radiation therapy) other than alopecia must have resolved to Grade 1 or baseline before the first dose of study treatment

Sponsors & Collaborators

• Akamis Bio: lead

Study Sites (6)

University of Southern California (USC) - Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA

Santa Barbara, California, 93105, United States

Location

Moffitt-Advent Health Clinical Research Unit

Celebration, Florida, 34747, United States

Location

Ochsner Medical Center (OMC) - The Gayle and Tom Benson Cancer Center

New Orleans, Louisiana, 70121-2429, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Khalil DN, Prieto Gonzalez-Albo I, Rosen L, Lillie T, Stacey A, Parfitt L, Soff GA. A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies. Invest New Drugs. 2023 Apr;41(2):317-323. doi: 10.1007/s10637-023-01345-8. Epub 2023 Mar 10.

  PMID: 36897458 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma; Virus Diseases

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Infections

Study Design

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

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 12, 2019
• Study Start: January 23, 2020
• Primary Completion: August 31, 2023
• Study Completion: December 20, 2023
• Last Updated: March 24, 2025

Record last verified: 2024-08

Locations

US (6)