Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours

NCT05043714 | Completed Phase 1 FDA Drug

• 1 other identifier: NG-641-03
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a phase 1a/1b, multicentre, open-label, non-randomized study of NG-641 in combination with nivolumab (or standard of care PD-1 inhibition) in patients with metastatic or advanced epithelial tumours. The purpose is to characterize the safety and tolerability of NG-641 in combination with nivolumab in patients with metastatic or advanced epithelial tumours and to determine the recommended dose of NG-641 in combination with nivolumab for further development in patients with metastatic or advanced epithelial tumours

Conditions

Metastatic Cancer; Epithelial Tumor

Keywords

Metastatic Cancer; Epithelial Tumor; Viral vector; Advanced; PsiOxus

Outcome Measures

Primary Outcomes (1)

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

  Incidence of: adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation of study treatment or study discontinuation and AEs resulting in death and Incidence of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria

  30 days after last dose of study drug

Study Arms (1)

Intravenous

EXPERIMENTAL

Phase 1a Part A: One cycle (28 days) of NG-641 on Days 1, 3 and 5 and nivolumab on Day 15, followed by nivolumab every 4 weeks. Phase 1a Part B: NG-641 on Days 1, 3 and 5 and one nivolumab on Day 15 in each of up to eight 28-day cycles.

Biological: NG-641 in combination with Nivolumab

Interventions

NG-641 in combination with Nivolumab 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. Nivolumab is a human monoclonal antibody that targets the PD-1 cluster of differentiation 279 cell surface membrane receptor.

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:
• Patients must have histologically or cytologically documented metastatic/advanced epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.
• At least one measurable site of disease according to RECIST Version 1.1 criteria; this lesion must be either (i) outside a previously irradiated area or (ii) progressive if it is in a previously irradiated area
• Tumour accessible for biopsy, biopsy deemed safe by the Investigator, and patient willing to consent to tumour biopsies
• All patients:
• Provide written informed consent to participate
• 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
• 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 allogeneic 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 long-term systemic immunosuppressive treatment
• Treatment with any live, live-attenuated or COVID-19 vaccine in the 30 days before the first dose of NG-641 or nivolumab
• Treatment with any other vaccine (including known non-live/live-attenuated and 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 (or risk factors for gastrointestinal bleeding), haemoptysis, or any history of bleeding requiring an investigative procedure, transfusion or hospitalisation in the 6 months before the first dose of study treatment

Sponsors & Collaborators

• Akamis Bio: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

Providence Medical Foundation

Fullerton, California, 92835, United States

Location

UCLA Department of Medicine

Santa Monica, California, 90404, United States

Location

Moffitt-Advent Health Clinical Research Unit

Celebration, Florida, 34747, United States

Location

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, Lancashire, L7 8YA, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, Oxfordshire, OX3 7LE, United Kingdom

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

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christian Ottensmeier, MD

  Clatterbridge Cancer Centre

  PRINCIPAL INVESTIGATOR

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: September 2, 2021
• First Posted: September 14, 2021
• Study Start: December 1, 2021
• Primary Completion: November 13, 2023
• Study Completion: October 4, 2024
• Last Updated: March 24, 2025

Record last verified: 2024-08

Locations

GB (2); US (4)