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Locally Advanced or Metastatic Solid TumoursPhase 1/2DIRECT-01NCT03548467

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

A Phase 1/2 study testing VB10.NEO and Bempegaldesleukin in people with Locally Advanced or Metastatic Solid Tumours, run by Nykode Therapeutics ASA at 6 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
VB10.NEO and Bempegaldesleukin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
6 sitesGermany
Study dates
4 Apr 2018to 30 Jan 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
  • Other protocol defined inclusion exclusion criteria may apply

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Germany6 sites

  • Charité Research Organisation, Campus Benjamin Franklin

    Berlin

  • Krankenhaus Nordwest gGmbH

    Frankfurt, 60488

  • Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle (Saale)

    Halle

  • University Hospital Heidelberg, NCT, Im Neuenheimer Feld 460

    Heidelberg, 69120

  • Universitätsmedizin Mannheim

    Mannheim, 68167

  • Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie

    Munich, 81675

Other trials in Germany

About this study

Official title: 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

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.

Read the 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.

Being tested
VB10.NEO, Bempegaldesleukin
Keywords
melanoma, NSCLC, clear renal cell carcinoma, urothelial cancer or SCCHN
Medical subject headings
Melanoma, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VB10.NEOBiological

    VB10.NEO is a vaccine and is supplied as a sterile, ready to use solution (14 vaccinations will be given).

  • BempegaldesleukinDrug

    Also called NKTR-214

    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.

Study groups in NCT03548467
Study groupRoleWhat they receive
VB10.NEO interventionExperimentalTreatment 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.
Receives: Biological: VB10.NEO
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.
Receives: Biological: VB10.NEO; Drug: Bempegaldesleukin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 24 months

Secondary outcomes (5)

  1. Immunogenicity by T-cell activity to each neoepitope of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214)

    Descriptive analyses for each patient of the immune-response to each neoepiotope

    Measured: Up to 24 months

  2. Objective Response Rate (ORR)

    Description of tumor response by iRECIST at regular intervals

    Measured: Up to 24 months

  3. Duration of Response (DOR)

    Descriptive analysis of DOR by iRECIST at regular intervals

    Measured: Up to 24 months

  4. Progression-free survival (PFS)

    Descriptive analysis of PFS by iRECIST at regular intervals

    Measured: Up to 24 months

  5. Survival at end of treatment (EoT) and end of study (EoS)

    Proportion of patients who are alive at EoT and EoS

    Measured: At 14 months and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2018
  2. Study start4 Apr 2018
  3. Primary completion30 Jan 2023
  4. Study completion30 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Open Label
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03548467
Sponsor's protocol ID
VB N-01
Acronym
DIRECT-01
Status last verified
Apr 2023
First submitted
17 Apr 2018
Last updated
21 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34311780

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VB10.NEO and Bempegaldesleukin in people with Locally Advanced or Metastatic Solid Tumours, run by Nykode Therapeutics ASA at 6 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Adverse Events including SAEs (Safety/tolerability) of VB10.NEO and the combination of VB10.NEO and bempegaldesleukin (NKTR-214) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03548467, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023; AzTrials last refreshed its copy on 4 Nov 2026.

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