Trial Title:
Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma
NCT ID:
NCT06016920
Condition:
HPV Positive Oropharyngeal Squamous Cell Carcinoma
HNSCC
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Pembrolizumab
Conditions: Keywords:
Unresectable
recurrent
metastatic
HPV16 positive
PD-L1
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Dose-finding trial, including a dose escalation phase (phase 1) where participants are
allocated sequentially to one of the 3 escalating doses; and a dose expansion phase
(phase 2a) where participants are randomized to one of two doses
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
VB10.16
Description:
Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) starting at Week
1/Day 1 during a 12-week induction period, followed by a maintenance period with
administrations every 6 weeks (Q6W) from Week 13 until Week 48. A total of up to 10 i.m.
administrations will be given.
VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.
Arm group label:
Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
Arm group label:
Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab 200 mg intravenous (i.v.) will be given in accordance with the local
regulatory-approved label Q3W starting at Week 1/Day 1 for as long as the patient
tolerates and continues to have clinical benefit from the treatment based on the patient
and investigator's decision, up to a maximum of 35 treatments corresponding to
approximately 2 years of treatment.
After 48 weeks of treatment patients can continue on 200 mg Q3W or change to 400 mg Q6W
at the discretion of the investigator and after consultation with the sponsor.
Pembrolizumab will be given by i.v. infusion over 30 minutes.
Arm group label:
Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
Arm group label:
Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
Arm group label:
Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
Other name:
KEYTRUDA®
Summary:
This is a multi-center study in patients with un-resectable Recurrent or Metastatic
HPV16-positive oropharyngeal Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is
designed to investigate VB10.16, an investigational therapeutic DNA vaccine in
combination with another medicine, pembrolizumab, which is the standard of care for
patients with previously untreated metastatic or resectable recurrent PD-L1 positive
HNSCC. The study is divided in 2 parts: a phase 1, dose escalation part, testing 3
different doses of VB10.16 in combination with a standard fixed dose of pembrolizumab.
The goal of this part is to evaluate the safety and tolerability of the combined
treatment and to decide on the dose of VB10.16 to be used in the second part of the
trial. In the second part of the trial, a phase 2a, dose expansion part, participants
will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg dose both in
combination with pembrolizumab. The dose given to each participant will be decided in
random.
The trial is designed to define the optimal dose of VB10.16 in combination with
pembrolizumab for future clinical studies based on the safety, tolerability and
anti-tumor effect data generated.
Detailed description:
This phase 1/2a, open-label, dose-finding trial is designed to evaluate the safety,
tolerability, immunogenicity, and anti-tumor activity of VB10.16 immunotherapy in
patients with HPV16-positive R/M oropharyngeal HNSCC whose tumors express PDL1 (CPS ≥ 1)
and who are eligible for pembrolizumab monotherapy as standard of care. The trial is
designed to determine the biological optimal dose (BOD) of VB10.16 in combination with a
fixed dose of pembrolizumab based on the totality of data (i.e., safety, tolerability,
anti-tumor activity, and HPV16 E6/E7specific cellular immune response). The trial
consists of 2 consecutive phases with separate patient groups in a seamless trial design:
a dose escalation phase (phase 1) and a dose expansion phase (phase 2a). After completing
48 weeks of combination treatment, patients can either continue pembrolizumab treatment
with 200 mg Q3W administration or change to 400 mg Q6W administration at the discretion
of the investigator and after consultation with the Sponsor.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
GENERAL REQUIREMENTS
1. ≥18 years of age (or as per national legal age of trial consent, whichever is
higher) at date of signing the informed consent form (ICF)
2. Histologically or cytologically confirmed R/M HNSCC, located in the oropharynx,
considered incurable by local therapy and eligible for monotherapy with
pembrolizumab
3. HPV16 positivity of R/M oropharyngeal HNSCC confirmed by designated central
laboratory
4. PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.
5. Primary tumor location in the oropharynx.
6. At least 1 measurable lesion per RECIST 1.1
ORGAN FUNCTION
Overall function:
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
Hematological function:
8. Platelets ≥100 × 10^9/L (100,000/µL)
9. Neutrophils (absolute neutrophil count [ANC]) ≥1.5 × 10^9/L (1,500/µL)
10. Hemoglobin ≥5.6 mmol/L (9.0 g/dL)
Hepatic and hemostatic function:
11. Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome,
then direct BILI ≤2 × ULN) or direct bilirubin ≤ULN for participants with total
bilirubin levels >1.5 × ULN.
12. Aspartate transaminase (AST) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver
metastases.
13. Alanine transaminase (ALT) ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver
metastases.
14. Alkaline phosphatase ≤ 2.5 × ULN or ≤5 × ULN for a patient with liver metastases.
15. International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN unless the
patient is receiving anticoagulant therapy, in which case PT and partial
thromboplastin time (PTT)/activated PTT (aPTT) must be within therapeutic range of
intended use of anticoagulants.
Renal function:
16. Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m^2 using the
Cockroft-Gault formula
OTHER TRIAL REQUIREMENTS
17. Female patients of childbearing potential: negative serum pregnancy test (≤72 hours)
18. Female patients of childbearing potential must agree to use highly effective
contraception throughout the trial (14 days prior to initiation of treatment for
oral contraception), and for at least 120 days (according to the current version of
the IB for pembrolizumab) after the last dose of pembrolizumab and up to 6 months
after the last dose of VB10.16, whichever comes last.
Male patients must agree to use male condoms during intercourse throughout the
trial, and up to 3 months after the last dose of VB10.16, and must refrain from
sperm donation in the same period.
19. Patients capable of giving informed consent must provide signed and dated written
informed consent prior to initiation of any study-related procedures.
Exclusion Criteria:
HNSCC DISEASE
1. Has disease that is suitable for local therapy with curative intent
2. Has progressive disease ≤6 months after completion of curatively intended concurrent
chemoradiotherapy for locoregionally advanced R/M oropharyngeal HNSCC
3. Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any
histology)
4. Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the
opinion of the investigator
PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS
5. Has received prior palliative radiotherapy within 2 weeks of start of trial
treatment or has a prior history of radiation pneumonitis
6. Any prior investigational or approved systemic antineoplastic drug or invasive
medical device (including ICIs), either as monotherapy or as part of a combination
regimen administered in the R/M HNSCC setting
7. Prior solid organ or tissue transplantation (except corneal transplant)
8. Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
9. Prior chimeric antigen receptor T (CAR-T) cell therapy
10. Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or
other molecule with similar mechanism of action) that engages T-cells
11. Has received a live or live-attenuated vaccine within 30 days prior to the first
dose of trial intervention
12. Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
vaccine within 30 days prior to VB10.16 treatment start
13. Prior administration with a therapeutic HPV16 vaccine
14. Patients receiving systemic immunosuppression with immunosuppressive agents such as
cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α)
blockers for any concurrent condition
15. Chronic administration of systemic corticosteroids: prednisone >10 mg daily (or dose
equivalent)
16. Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or
plasma components ≤2 weeks prior to VB10.16 treatment start
17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor
(e.g., CTLA-4, OX 40, CD137)
18. Has received prior surgery within 4 weeks prior to treatment
19. Any planned major surgery
PRIOR OR CONCURRENT MORBIDITY
Malignancy:
20. Past or current malignancy other than inclusion diagnosis, except for:
- Malignancy treated with curative intent and with no known active disease
present and has not received chemotherapy for at least 3 years before screening
and felt to be at low risk for recurrence by the treating physician
- Adequately treated breast ductal carcinoma in situ without evidence of disease
- Adequately treated cervical carcinoma in situ, without evidence of disease
- Adequately treated non-melanoma skin cancer without evidence of disease
- Adequately treated superficial or in situ carcinoma of the bladder without
evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
Hepatic and hemostatic function:
21. Any current bleeding disorder, active bleeding, or bleeding diathesis
Cardiovascular function:
22. Symptomatic congestive heart failure (Grade III or IV as classified by the New York
Heart Association), unstable angina pectoris, or cardiac arrhythmia
23. History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start
24. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood
pressure ≥100 mmHg), despite optimal medical management
25. Any other significant cardiac disease(s) that, in the opinion of the investigator,
is/are clinically significant and/or unacceptable
Pulmonary function:
26. Has a history of (non-infectious) pneumonitis / interstitial lung disease that
required steroids or has current pneumonitis / interstitial lung disease
Immune system and infectious diseases:
27. Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of
immunosuppression
28. Has an active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed
29. Has a known history of human immunodeficiency virus (HIV) infection.
30. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active
Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
31. Any active, acute, or chronic infection that is uncontrolled and/or requires
systemic treatment
32. Known allergies, sensitivity, or intolerance to VB10.16 (active substance or to any
of the excipients), pembrolizumab (active substance or to any of the excipients), or
aminoglycosides (especially kanamycin).
Central nervous system (CNS) function:
33. Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or
stroke
34. Has known active CNS metastases and/or carcinomatous meningitis. Patients with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during trial screening),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to first dose of trial treatment
35. New (≤6 months), progressive and/or symptomatic brain metastases
OTHER
36. Is currently participating in or has participated in a trial of an investigational
agent or device in the R/M setting.
37. Has a history or current evidence of any condition, therapy, or laboratory
abnormality, or other circumstance that might confound the results of the trial or
interfere with the patient's participation for the full duration of the trial, such
that it is not in the best interest of the patient to participate, in the opinion of
the treating investigator
38. Has a known psychiatric or substance abuse disorder that would interfere with the
patient's ability to cooperate with the requirements of the trial
39. Has a concomitant medical condition requiring receipt of a therapeutic anticoagulant
that, in the opinion of the treating physician, would contraindicate administration
of VB10.16 and tumor biopsies
40. Female patients who are pregnant or breastfeeding
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fakultni nemocnice Olomouc, Olomuoc
Address:
City:
Olomouc
Country:
Czechia
Status:
Recruiting
Contact:
Last name:
Melichar Bohuslav
Facility:
Name:
Hospices Civils De Lyon
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Jonathan Thouvenin
Facility:
Name:
Hôpital de la Pitié - Salpétrière in Paris
Address:
City:
Paris
Zip:
75013
Country:
France
Status:
Recruiting
Contact:
Last name:
Jean-Philippe Spano
Investigator:
Last name:
Spano
Email:
Principal Investigator
Facility:
Name:
Institut Gustave Roussy, Paris
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Caroline Even
Facility:
Name:
Universität Leipzig Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde
Address:
City:
Leipzig
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Andreas Dietz
Facility:
Name:
Orszagos Onkologiai Intezet, Budapest
Address:
City:
Budapest
Country:
Hungary
Status:
Recruiting
Contact:
Last name:
Erika Hitre, MD
Facility:
Name:
University of Bergen, Haukeland University Hospital
Address:
City:
Bergen
Country:
Norway
Status:
Recruiting
Contact:
Last name:
Marianne Brydoy, MD
Facility:
Name:
Oslo Universitetssykehus
Address:
City:
Oslo
Country:
Norway
Status:
Recruiting
Contact:
Last name:
Åse Bratland, MD, PhD
Facility:
Name:
Uniwersyteckie Cetrum Kliniczne
Address:
City:
Gdańsk
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Rafal Dziadziusczko, Dr
Facility:
Name:
Narodowy Instytut Onkologii-im Marii Sklodowskiej-Curie Panstwowy Instytut
Address:
City:
Gliwice
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Tomasz Rutkowski, Dr
Facility:
Name:
KO-MED Centra Kliniczne Lublin II, Lublin
Address:
City:
Lublin
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Ludmilla Grzybowska - Szatkowska
Facility:
Name:
Hospital del Mar, Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marta Guix Arnau
Facility:
Name:
Institut Catala d'Oncologia, Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marc Oliva
Facility:
Name:
Hospital Universitario Virgen de las Nieves, Granada
Address:
City:
Granada
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Juaquina Martin Galan
Facility:
Name:
MD Anderson Cancer Center, Madrid
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Pilar López Criado
Facility:
Name:
East and North Hertfordshire NHS Trust Mount Vernon Hospital
Address:
City:
London
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Saira Khalique, Dr
Start date:
December 19, 2023
Completion date:
January 2028
Lead sponsor:
Agency:
Nykode Therapeutics ASA
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Nykode Therapeutics ASA
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06016920
