A Study to Evaluate Safety and Efficacy of Multiple Dosing With VB10.NEO and Bempegaldesleukin (NKTR-214) Immunotherapy in Patients With Locally Advanced or Metastatic Cancer
- Conditions
- Locally Advanced or Metastatic Solid Tumours
- Interventions
- Biological: VB10.NEO
- Registration Number
- NCT03548467
- Lead Sponsor
- Nykode Therapeutics ASA
- Brief Summary
This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO and bempegaldesleukin (NKTR-214) immunotherapy in patients with locally advanced or metastatic solid tumours.
- Detailed Description
This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO immunotherapy in patients with locally advanced or metastatic solid tumours including melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN), who did not reach complete responses with immune checkpoint inhibitor (CPI) therapy as their standard of care (SOC) treatment.
Patients with melanoma, NSCLC, RCC and urothelial carcinoma must upon screening, have been receiving a CPI (anti-PD-1 or anti-PD-L1) for at least 12 weeks as the patient's standard of care. Patients with SCCHN can be screened as long as they have initiated treatment with CPI as SOC. The VB10.NEO vaccine will be added to continuing CPI treatment and shall not replace, omit, postpone or terminate the standard therapy. Patients who have been treated with CPI for at least 12 weeks, will be enrolled in case of some benefit to CPI treatment is expected, as defined by partial response, stable disease or disease progression (in case of a mixed response to CPI, provided at least one lesion shows measurable regression and patient, according to the investigator, would have a clinical benefit of continued immunotherapy).
The assumption is to combine the immuno-stimulating effect of CPIs with immune responses towards specific neo-antigens in the vaccine, which may possibly increase the anti-tumour effect to reach durable efficacy.
One arm of the study patients with SCCHN will have the option to be treated with bempegaldesleukin (NKTR-214) in combination with personalised VB10.NEO. This arm is open for enrollment from November 2019.
The study will be conducted in two parts. Part A will evaluate safety, feasibility and efficacy of individualised VB10.NEO and bempegaldesleukin (NKTR-214) immunotherapy in SCCHN patients. The expansion part B will explore efficacy and safety in further patients with selected types of cancer showing signs of efficacy during part A.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description VB10.NEO intervention VB10.NEO Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing to patients within the selected tumor types. VB10.NEO in combination with bempegaldesleukin (NKTR-214) VB10.NEO Bempegaldesleukin (NKTR-214) will be given in combination with VB10.NEO in up to 10 patients with SCCHN. Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing. Bempegaldesleukin (NKTR-214) will be given after at least 4 doses of VB10.NEO. VB10.NEO in combination with bempegaldesleukin (NKTR-214) Bempegaldesleukin Bempegaldesleukin (NKTR-214) will be given in combination with VB10.NEO in up to 10 patients with SCCHN. Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing. Bempegaldesleukin (NKTR-214) will be given after at least 4 doses of VB10.NEO.
- Primary Outcome Measures
Name Time Method Rate of Adverse Events including SAEs (Safety/tolerability) of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214) Up to 24 months Total number, severity (CTCAE grade) of adverse events (AEs), and if AE is leading to treatment discontinuation.
- Secondary Outcome Measures
Name Time Method Immunogenicity by T-cell activity to each neoepitope of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214) Up to 24 months Descriptive analyses for each patient of the immune-response to each neoepiotope
Objective Response Rate (ORR) Up to 24 months Description of tumor response by iRECIST at regular intervals
Duration of Response (DOR) Up to 24 months Descriptive analysis of DOR by iRECIST at regular intervals
Progression-free survival (PFS) Up to 24 months Descriptive analysis of PFS by iRECIST at regular intervals
Survival at end of treatment (EoT) and end of study (EoS) At 14 months and 24 months Proportion of patients who are alive at EoT and EoS
Trial Locations
- Locations (6)
University Hospital Heidelberg, NCT, Im Neuenheimer Feld 460
🇩🇪Heidelberg, Germany
Universitätsmedizin Mannheim
🇩🇪Mannheim, Germany
Krankenhaus Nordwest gGmbH
🇩🇪Frankfurt, Germany
Charité Research Organisation, Campus Benjamin Franklin
🇩🇪Berlin, Germany
Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle (Saale)
🇩🇪Halle, Germany
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie
🇩🇪Munich, Germany