Description:
To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.
To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced epithelial tumours.
Recruiting
Phase 1
Drug | Synonyms | Arms |
---|---|---|
NG-641 | Intratumoural | |
NG-641 | Intravenous |
To characterise the safety and tolerability of NG-641 in patients with metastatic or advanced
epithelial tumours.
The Phase Ia part of the study is a dose escalation and dose expansion phase investigating
NG-641 administration by intratumorural injection (IT) and intravenous (IV) infusion in a
range of tumour types
The Phase Ib part of the study is to investigate safety and efficacy of NG-641 as monotherapy
or in combination with chemotherapy agents and/or checkpoint inhibitors in separate efficacy
cohorts of patients with specific epithelial tumour types.
Name | Type | Description | Interventions |
---|---|---|---|
Intratumoural | Experimental | In the IT cohort, patients will receive a single dose of NG-641 by IT injection on Day 1. The dose given to each patient will be dependent on the size of the tumour lesion to be injected. |
|
Intravenous | Experimental | In the IV cohort, patients will receive a single cycle of study treatment, with three single doses of NG-641 on Days 1, 3 and 5 by IV infusion. |
|
Inclusion Criteria: 1. Histologically or cytologically documented advanced or metastatic epithelial cancer that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available 2. Provide written informed consent to participate 3. Aged 18 years or over 4. a) For patients undergoing surgical excision/resection of tumour lesion(s): - Tumour deemed accessible and safe for biopsy by the Investigator - Patient able to undergo surgical procedure and appropriate anaesthesia - Willing to consent for baseline biopsies and surgical procedure b) For patients not undergoing surgical excision/resection: - Tumour accessible for biopsy and a biopsy deemed safe by the Investigator - Willing to consent to tumour biopsies 5. ECOG performance status 0 or 1 6. Predicted life expectancy of 3 months or more 7. Ability to comply with study procedures in the Investigator's opinion 8. Adequate renal function 9. Adequate hepatic function 10. Adequate bone marrow function 11. Prothrombin time and aPTT time within normal range and international normalised ratio ≤1.5, as appropriate 12. Meeting reproductive status requirements 13. Phase Ia - Dose Expansion Phase only: at least one measurable site of disease according to RECIST Version 1.1 criteria Exclusion Criteria: 1. Known history or evidence of significant immunodeficiency due to underlying illness 2. Splenectomy 3. Active infections requiring antibiotics, physician monitoring or recurrent fevers (>38.0˚C) associated with a clinical diagnosis of active infection 4. Active viral disease or positive test for hepatitis B virus using hepatitis B surface antigen test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. Positive test for HIV or AIDS. Viral serology testing is not required in the absence of history 5. History of chronic liver disease or evidence of hepatic cirrhosis 6. History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organising pneumonia (bronchiolitis obliterans, cryptogenic organising pneumonia, etc.) 7. Use of the following antiviral agents: ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to the first dose of study treatment; or pegylated interferon in the 4 weeks before the first dose of study treatment 8. Incomplete recovery from surgery, incomplete healing of an incision site or evidence of infection 9. Any of the following in the 3 months before the first dose of study treatment: Grade 3 or 4 gastrointestinal bleeding/haemorrhage (unless due to resected tumour), treatment-resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thrombo-embolic event, history or evidence of haemoptysis or menorrhagia 10. History of myocardial infarction or significant cardiovascular or cerebrovascular event in the 6 months before the first dose of study treatment 11. History of DVT or pulmonary embolus in the 12 months before the first dose of study treatment 12. History of significant bleeding requiring hospitalisation in the 12 months before the first dose of study treatment 13. Patients receiving therapeutic or prophylactic anticoagulation therapy 14. Treatment with PD-1/programmed death ligand (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), or any other (including experimental) immune checkpoint inhibitor or immune-stimulatory treatment in the 6 weeks before the first dose of study treatment 15. 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 16. Other prior malignancy active within the previous 3 years except for local or organ confined early stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual disease and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety 17. Symptomatic brain metastases or any leptomeningeal metastases that are symptomatic and/or requires treatment. Patients with brain metastases are eligible if these have been treated (surgery, radiotherapy) 18. Penetrating tumour infiltration of major blood vessels, pericardium, gastrointestinal tract or other hollow organs that may lead to perforation due to tumour necrosis 19. Patients at an increased risk due to tumour flare, as assessed by the Investigator (e.g. an initial increase in tumour size that may lead to intestinal obstruction, obstruction of the ureter or airway) 20. Lymphangitic carcinomatosis 21. Any history of renal disease or renal injury, coagulopathy or autoimmune disease 22. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator or the Medical Monitor, may increase the risk associated with study participation or study treatment administration, impair the ability of the patient to receive protocol therapy or interfere with the interpretation of study results 23. Previous treatment with enadenotucirev or FAP targeting agents 24. Known allergy to NG-641 transgene products or formulation 25. Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Measure: | Incidence of adverse events (safety and tolerability) in study NG-641 |
Time Frame: | End of study treatment visit, Day 85 |
Safety Issue: | |
Description: | Assess the safety and tolerability of NG-641 by review of adverse events including serious adverse events (SAEs), adverse events meeting protocol defined DLT criteria, severe adverse events, adverse events leading to study treatment or study discontinuation, and adverse events resulting in death. |
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | PsiOxus Therapeutics Ltd |
March 16, 2021