NCT05043714

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

A Multicentre, Open-label, Non-randomized, Phase 1a/1b Study of NG-641, a Tumour-selective and Transgene-expressing Adenoviral Vector, in Combination With Nivolumab (or Standard of Care PD-1 Inhibition) in Patients With Metastatic or Advanced Epithelial Tumours (NEBULA)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Akamis Bio · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Detailed description

The Phase 1a part of the study is a dose escalation phase and is composed of two parts: Part A, which is investigating NG-641 administration (single cycle) by intravenous (IV) infusion in combination with up to 8 cycles of nivolumab; and Part B, which is investigating multicycle NG-641 administration (up to 8 cycles) by IV infusion in combination with up to 8 cycles of nivolumab. Both parts will include patients with metastatic or advanced tumours. Part B will open once a recommended starting dose of NG-641 is identified from the single-cycle dose escalation. Dose escalation in Part A may continue in parallel once Part B has opened. The Phase 1b part of the study will further investigate the efficacy and safety of the selected dose regimen in up to three of the tumour types evaluated in phase 1b (tumour-specific Dose Expansion Cohorts A, B and C). A Simon 2-stage design will be used, with sample size calculations and futility criteria specific to each individual expansion cohort. Patients enrolled in Cohort A will have recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) that is considered incurable by local therapies and has been recently treated with a first-line platinum-based chemotherapy regimen or platinum-based chemotherapy plus pembrolizumab. Patients enrolled in Cohort A will be subdivided in to two groups according to whether they have received prior anti-PD-1 therapy (Cohort A1, chemotherapy regimen without pembrolizumab; Cohort A2, chemotherapy regimen with pembrolizumab) with each sub-cohort using a separate Simon 2-stage model. Patients in Cohort A2 who are already receiving pembrolizumab as standard of care at enrolment may continue this background treatment in combination with the recommended NG-641 dose; patients are permitted to switch to nivolumab at the Investigator's discretion. Cohorts B and C will be defined in a future protocol update that will be submitted for approval prior to these cohorts opening. Following treatment, patients will be followed every 8 weeks until 12 months from first dose for disease status, overall survival, further cancer therapy and the best response and date of disease progression on further cancer therapy. These assessments may be performed by telephone calls or at routine visits to the hospital.

Conditions

• Metastatic Cancer
• Epithelial Tumor

Interventions

Type	Name	Description
BIOLOGICAL	NG-641 in combination with Nivolumab	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.

Timeline

• Start date: 2021-12-01
• Primary completion: 2023-11-13
• Completion: 2024-10-04
• First posted: 2021-09-14
• Last updated: 2025-03-24

Locations

6 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study