A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck

NCT04830592 | Completed Phase 1 DMC

• 1 other identifier: NG-641-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

A multicentre, open-label, non-randomized, phase Ib neoadjuvant study of intravenous NG-641, as monotherapy or in combination with pembrolizumab, in patients with surgically resectable squamous cell carcinoma of the head and neck (SCCHN).

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Squamous cell carcinoma of the head and neck; SCCHN; NG-641; Pembrolizumab; Akamis Bio

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (safety and tolerability)

  Assess the safety and tolerability of NG-641 by review of adverse events (AEs), serious adverse events, AEs resulting in delays to planned surgery, AEs leading to study treatment or study discontinuation and AEs resulting in death.

  End of Study Treatment Visit (Day 57)

Study Arms (2)

Part A

EXPERIMENTAL

NG-641 monotherapy

Biological: NG-641

Part B

EXPERIMENTAL

NG-641 and pembrolizumab

Biological: NG-641; Biological: Pembrolizumab

Interventions

NG-641 BIOLOGICAL

Patients receive three doses of NG-641 by intravenous infusion. 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.

Part A; Part B

Pembrolizumab BIOLOGICAL

Patients receive three doses of NG-641 by intravenous infusion and a single dose of Pembrolizumab by intravenous infusion.

Part B

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed or recurrence of clinical stage III-IVb, histologically confirmed oral cavity, larynx, hypopharynx or oropharynx SCCHN (T1 with N2-3; T2 with N2-3; T3 with N0-3; T4a with N0-3)
• Disease is considered resectable, definitive surgery is planned in the next 8 weeks from screening, and the patient is willing to undergo surgery (potential for 2-3 cm of resected tumour specimen to be available for translational research purposes)
• Provide written informed consent to participate
• Aged 18 years or over
• Willing to consent to tumour biopsies at baseline
• ECOG performance status 0 or 1
• Ability to comply with study procedures in the Investigator's opinion
• Adequate renal function
• Adequate hepatic function
• Adequate bone marrow function
• Meeting reproductive status requirements

You may not qualify if:

• Prior allogeneic or autologous bone marrow or organ transplantation
• Active infections requiring antibiotics, physician monitoring or recurrent fevers (\>38.0˚C) associated with a clinical diagnosis of active infection. Active infection requiring systemic therapy within 1 week of the anticipated first dose of study drug
• Active viral disease or positive test for hepatitis B virus, hepatitis C virus (HCV) or HIV/AIDS
• Patients who have active 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 (see protocol for full criteria)
• Treatment with any COVID-19 vaccine in the 28 days before the first dose of NG-641, unless the vaccine is known to not be based on an adenoviral vector (e.g., mRNA vaccines)
• Treatment with any vaccine (including known non-adenoviral COVID-19 vaccines) in the 7 days before first dose of NG-641
• History of clinically significant chronic liver disease
• History of clinically significant interstitial lung disease (including pneumonitis)
• History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment
• Use of antiviral agents
• Incomplete recovery from surgery, incomplete healing of an incision site or evidence of infection
• Any of the following in the 3 months before the first dose of study treatment: Grade 3 or 4 gastrointestinal bleeding or risk factors for gastrointestinal bleeding, infectious or inflammatory bowel disease, pulmonary embolism or other uncontrolled thromboembolic event, history or evidence of haemoptysis, or significant cardiovascular or cerebrovascular event
• Any known Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 coagulation abnormality/coagulopathy
• Prior history of bowel obstruction, or infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment
• Major surgery or treatment with any chemotherapy, radiation therapy, biologics for cancer or investigational drug/therapy in the 28 days before the first dose of study treatment:

Sponsors & Collaborators

• Akamis Bio: lead

Study Sites (4)

Cardiff & Vale University LHB

Cardiff, United Kingdom

Location

The Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

The Royal Marsden Hospital

London, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, 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

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Christian Ottensmeier, Prof.

  The Clatterbridge Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 5, 2021
• Study Start: November 4, 2021
• Primary Completion: December 7, 2023
• Study Completion: October 4, 2024
• Last Updated: March 24, 2025

Record last verified: 2024-08

Locations

GB (4)