Locally advanced or metastatic solid tumours including melanoma, NSCLC, clear renal cell carcinoma, urothelial cancer or SCCHN MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts
Conditions
Interventions
Product Name: VB10.NEO
Product Code: pVB10.NEO
Pharmaceutical Form: Solution for injection in needle-free injector
INN or Proposed INN: pVB10.NEO
Current Sponsor code: VB10.NEO
Other descriptive name
Sponsors
Nykode Therapeutics AS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For patients with melanoma: 1. Have histologically confirmed locally advanced or metastatic melanoma not amenable to local treatment 2. Patients must be on CPI (i.e. anti-programmed cell death protein 1 [anti-PD-1] or anti-programmed cell death protein ligand 1[anti-PD-L1]) or must initiate treatment with CPI (e.g. nivolumab or pembrolizumab) as part of their cancer treatment as prescribed by the treating physician For patients with lung cancer: 1. Have histologically confirmed locally advanced or metastatic NSCLC not amenable to local treatment 2. Patients must have been on CPI (i.e. anti-PD1 or anti-PD-L1) for at least 12 weeks before screening and must be on CPI treatment as part of their cancer treatment as prescribed by the treating physician, n, e.g. nivolumab, pembrolizumab, atezolizumab or durvalumab. For patients with renal cancer: 1. Have histologically confirmed locally advanced or metastatic clear RCC not amenable to local treatment 2. Patients must have been on CPI (i.e. anti-PD1 or anti-PD-L1) for at least 12 weeks before screening and must be on CPI treatment as part of their cancer treatment as prescribed by the treating physician, e.g. nivolumab For patients with urothelial carcinoma: 1. Have histologically confirmed locally advanced or metastatic urothelial carcinoma not amenable to local treatment 2. Patients must have been on CPI (i.e. anti-PD1 or anti-PD-L1) for at least 12 weeks before screening and must be on CPI treatment as part of their cancer treatment as prescribed by the treating physician, e.g. nivolumab, pembrolizumab or atezolizumab Inclusion criteria for patients with head and neck cancer: 1. Have histologically confirmed locally advanced or metastatic SCCHN not amenable to local treatment. 2. Patients must be on CPI (i.e. anti-PD-1 or anti-PD-L1) or must initiate treatment with CPI at screening as part of their cancer treatment as prescribed by the treating physician, e.g. nivolumab or pembrolizumab. Inclusion criteria for patients in all arms: 3. 18 years or older 4. Patients who have been on CPI for longer than 12 weeks at screening need to be per RECIST: a. in partial response or b. stable disease or c. in progression, i.e. in case of a mixed response to CPI treatment, provided that at least 1 lesion shows measurable regression and who, according to the investigator, have a clinical benefit of continued immunotherapy. 5. Adequate tumour specimen (at least 1 core biopsy) must be available for exome sequencing, preferably a newly acquired FF sample. Archival FFPE samples from biopsies or resected tumour material taken =65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: 1. Ocular melanoma 2. Brain metastases (unless treated, controlled, stable for at least 6 weeks) or leptomeningeal spread of disease 3. Positive serological test for hepatitis B or C virus surface antigen or HIV 4. Other concomitant or prior malignant disease except for adequately treated basal cell carcinoma or other non-melanomatous skin cancer, low-grade urothelial cancer or other malignancies treated with curative intent within 2 or more years pre-study entry and in complete remission at study entry 5. Immune disorder requiring the continued use (> 7 days) of high-dose systemic steroids or immunosuppressive agents for any concurrent condition, or a documented history of clinically significant autoimmune disease, as assessed by the investigator. Systemically administered corticosteroids must be discontinued > 4 weeks prior to first study vaccine administration. Exclusion criteria 6 deleted. 7. Known allergy to aminoglycosides or to any of the IMP’s components/excipients Exclusion criteria 8 deleted. 9. History of toxic shock syndrome 10. Evidence or history of clinically significant cardiac disease including congestive heart failure, unstable angina, acute myocardial infarction or cerebrovascular accident within the last 6 months, and symptomatic arrhythmia requiring therapy 11. Ongoing toxicity from prior therapy that is > Grade 2 for skin toxicities and > Grade 1 for all other toxicities, or that is progressing in severity, except toxicities not considered a safety risk 12. History of life-threatening organ toxicity of Grade 4 related to CPI exposure, excluding endocrinopathies 13. Acute infections 14. Active lesions/rashes or any implantable devices within 2cm of the site of vaccination 15. Current participation in a clinical trial (allowed if not exposed to IMP) 16. Planned vaccination against infections within 30 days before start of treatment. 17. Previous transplantations 18. Inadequate bone marrow function: Platelet count 1.5 x ULN for the institution; patients with Gilbert’s Syndrome >3 x ULN • AST or ALT >3 x ULN; patients with liver metastases > 5 x ULN • By the investigator's judgement, patients exceeding the above limits as an effect of CPI treatment should be excluded; patients exceeding the above limits due to the course of malignancy may be enrolled 21. Inadequate renal function: • Estimated CrCl of =30 mL/min • Proteinuria >100 mg/dL 22. Clinically significant uncorrected electrolyte abnormalities that are CTCAE Grade 3 or higher for both low and high values 23. Female patients of childbearing potential not willing to use a highly effective form of contraception during treatment and for at least 6 months after the last dose of VB10.NEO or NKTR-214 24. Pregnancy or intention to become pregnant during the study period (serum/urine pregnancy test: screening, day of vaccination, prior to treatment start) 25. Nursing women 26. Evidence of any other medical conditions that may interfere with study participation, affect patient compliance or place the patient at high risk from treatment-related complications Exclusion criteria for patients enrolled to arm 5B: 27.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety/tolerability of multiple doses of 3 mg VB10.NEO immunotherapy and of multiple doses of 3 mg VB10.NEO immunotherapy in combination with 0.006 mg/kg bempegaldesleukin. To determine the feasibility of VB10.NEO (overall process feasibility from biopsy, sequencing, neoepitope selection and vaccine manufacturing).;Secondary Objective: To assess the immunogenicity of multiple doses of 3 mg VB10.NEO immunotherapy and of multiple doses of 3 mg VB10.NEO immunotherapy in combination with 0.006 mg/kg bempegaldesleukin. To make additional preliminary assessments of the efficacy of multiple doses of 3 mg VB10.NEO immunotherapy and of multiple doses of 3 mg VB10.NEO immunotherapy in combination with 0.006 mg/kg bempegaldesleukin. ;Primary end point(s): Safety/Tolerability: • Rate of adverse events (AEs) including serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) and CTCAE grade - total number and severity - leading to treatment discontinuation • Results of physical examinations and vital signs • Results of safety laboratory • Changes in ECOG performance status • Changes in electrocardiogram (ECG) results Feasibility: Duration of manufacturing time for VB10.NEO drug products and failure to treat (feasibility).;Timepoint(s) of evaluation of this end point: Extent of exposure will be described by whether the patient took any investigational product along with the number of days of exposure (last date of dosing minus first day of dosing plus 1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Immunogenicity, Biomarkers and Cytokines: • Descriptive analysis of the cellular immune response against the individual neoepitopes (enzyme-linked immunospot assay). • Descriptive analysis of potential predictive biomarkers for immunological activity or clinical efficacy. • Descriptive analysis of proteomics. • Descriptive analysis of the development of the mutagenic landscape over time. • Descriptive analysis of the fine characterisation of neoantigen-specific T cells (for patients in arms 5A and 5B). • Descriptive analysis of the flow cytometry to analyse changes in markers of immune cell populations, including, but not limited to, markers for T lymphocytes, regulatory T cells, and T cell activation. Efficacy: Description of early signs of efficacy of VB10.NEO and NKTR-214 immunotherapy by means of: • Objective Response Rate (ORR) • Duration of Response (DOR) • Progression-free survival (PFS) • Overall survival (OS) • Lesion development over time ;Timepoint(s) of evaluation of this end point: Efficacy analyses will be done separately for each tumour entity-specific cohort. The efficacy endpoints will be analysed descriptively including 95% confidence intervals for proportions wherever applicable. | — |
Countries
Germany
Contacts
Public ContactMedical Expert
Nykode Therapeutics AS
Outcome results
None listed