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
DIRECT-01
An Open Labelled First Human Dose Phase 1/2a Study to Evaluate Safety, Feasibility, Efficacy of Multiple Dosing With Individualised VB10.NEO and Bempegaldesleukin (NKTR-214) Immunotherapy in Patients With Locally Advanced or Metastatic Melanoma, Non-small Cell Lung Cancer (NSCLC), Clear Renal Cell Carcinoma, Urothelial Cancer or Squamous Cell Carcinoma of Head and Neck, Who Did Not Reach Complete Responses With Current Standard of Care Immune Checkpoint Blockade
1 other identifier
interventional
41
1 country
6
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2018
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 4, 2018
CompletedFirst Submitted
Initial submission to the registry
April 17, 2018
CompletedFirst Posted
Study publicly available on registry
June 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2023
CompletedApril 21, 2023
April 1, 2023
4.8 years
April 17, 2018
April 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Adverse Events including SAEs (Safety/tolerability) of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214)
Total number, severity (CTCAE grade) of adverse events (AEs), and if AE is leading to treatment discontinuation.
Up to 24 months
Secondary Outcomes (5)
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
Objective Response Rate (ORR)
Up to 24 months
Duration of Response (DOR)
Up to 24 months
Progression-free survival (PFS)
Up to 24 months
Survival at end of treatment (EoT) and end of study (EoS)
At 14 months and 24 months
Study Arms (2)
VB10.NEO intervention
EXPERIMENTALTreatment 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)
EXPERIMENTALBempegaldesleukin (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.
Interventions
VB10.NEO is a vaccine and is supplied as a sterile, ready to use solution (14 vaccinations will be given).
0.006 mg/kg bempegaldesleukin (NKTR-214) will be administered intravenously q4w for up to 11 doses starting from week 11 or at any dosing visit up to week 34 and for up to week 50 (up to 11 doses). The first 2 doses will be in a Q3W interval and following doses in Q4W intervals.
Eligibility Criteria
You may qualify if:
- Have histologically confirmed locally advanced or metastatic melanoma, NSCLC, RCC, urothelial carcinoma or SCCHN.
- Patients must have been on CPI (i.e., anti-PD-1 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.
- Patients must be on CPI or must initiate treatment with CPI at screening as part of their cancer treatment.
- All arms
- Patients who have been on CPI for longer than 12 weeks at screening need to be per RECIST:
- in partial response or;
- stable disease or,
- in progression, i.e., in case of a mixed response to CPI, provided at least one lesion shows measurable regression and who, according to the investigator, have a clinical benefit of continued immunotherapy.
- Adequate tumour specimen must be available for exome sequencing.
- Measurable disease per RECIST 1.1 criteria.
- ECOG performance status ≤ 1.
- Life expectancy at least 6 months in the best judgement of the investigator.
- Willing and able to sign a written informed consent form.
You may not qualify if:
- Ocular melanoma.
- Brain metastases (unless controlled and stable for at least 6 weeks) or leptomeningeal spread of disease.
- Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV).
- 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
- Patients who have an active, known or suspected autoimmune disease. Patients having required systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that require systemic steroids or immunosuppressive agents (Exceptions include any patient on 10 mg or less of prednisolone or equivalent, patients with vitiligo, hypothyroidism stable on hormone replacement; type 1 diabetes, Grave's disease, Hashimoto's disease, alopecia areata, eczema).
- Immunosuppression including the continued use (\> 7 days) of high-dose (\>10 mg of prednisolone or equivalents) systemic steroids or the use of immunosuppressive agents for any concurrent condition.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nykode Therapeutics ASAlead
- Nektar Therapeuticscollaborator
- Vaccibody AScollaborator
Study Sites (6)
Charité Research Organisation, Campus Benjamin Franklin
Berlin, Germany
Krankenhaus Nordwest gGmbH
Frankfurt, 60488, Germany
Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle (Saale)
Halle, Germany
University Hospital Heidelberg, NCT, Im Neuenheimer Feld 460
Heidelberg, 69120, Germany
Universitätsmedizin Mannheim
Mannheim, 68167, Germany
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie
Munich, 81675, Germany
Related Publications (1)
Srikrishna D, Sachsenmeier K. We need to bring R0 < 1 to treat cancer too. Genome Med. 2021 Jul 26;13(1):120. doi: 10.1186/s13073-021-00940-9.
PMID: 34311780DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 17, 2018
First Posted
June 7, 2018
Study Start
April 4, 2018
Primary Completion
January 30, 2023
Study Completion
January 30, 2023
Last Updated
April 21, 2023
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will not share