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Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma

Primary Purpose

HPV-Related Squamous Cell Carcinoma, HNSCC

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
VB10.16
Pembrolizumab
Sponsored by
Nykode Therapeutics ASA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV-Related Squamous Cell Carcinoma focused on measuring Unresectable, recurrent, metastatic, HPV16 positive, PD-L1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: GENERAL REQUIREMENTS ≥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) Histologically or cytologically confirmed R/M HNSCC considered incurable by local therapy and eligible for monotherapy with pembrolizumab HPV16 positivity of R/M HNSCC confirmed by designated central laboratory PD-L1 positivity (CPS ≥1) Must provide a tumor tissue sample collected prior to VB10.16 treatment initiation for baseline tumor microenvironment analyses Primary tumor location in the oropharynx, oral cavity, hypopharynx, or larynx At least 1 measurable lesion per RECIST 1.1 ORGAN FUNCTION Overall function: Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 Hematological function: Platelets 100 - 400 × 10^9/L (100,000 - 400,000/µL) Neutrophils (absolute neutrophil count [ANC]) ≥1.5 × 10^9/L (1,500/µL) Hemoglobin ≥5.6 mmol/L (9.0 g/dL) Hepatic and hemostatic function: Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome, then direct BILI ≤2 × ULN) Aspartate transaminase (AST) ≤ 2.5 × ULN Alanine transaminase (ALT) ≤ 2.5 × ULN Alkaline phosphatase ≤ 2.5 × ULN International normalized ratio (INR) ≤1.5 × ULN Renal function: Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m^2 using the Cockroft-Gault formula OTHER TRIAL REQUIREMENTS Female patients of childbearing potential: negative serum pregnancy test (≤72 hours) Female patients of childbearing potential and male patients must agree to use highly effective contraception, and male patients must refrain from sperm donation throughout the trial (14 days prior to initiation of treatment for oral contraception), and for at least 120 days (according to the latest country-specific pembrolizumab label) after the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16, whichever comes last 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 Has disease that is suitable for local therapy with curative intent Has progressive disease ≤6 months after completion of curatively intended systemic treatment for locoregionally advanced R/M HNSCC Primary tumor site of the nasopharynx (any histology) Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS Has received prior radiotherapy within 2 weeks of start of trial treatment or has had a history of radiation pneumonitis 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 Prior solid organ or tissue transplantation (except corneal transplant) Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) Prior chimeric antigen receptor T (CAR-T) cell therapy Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecule with similar mechanism of action) that engages T-cells Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start Prior administration with a therapeutic HPV16 vaccine Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α) blockers for any concurrent condition Chronic administration of systemic corticosteroids: prednisone >10 mg daily (or dose equivalent) or an average cumulative dose of >140 mg prednisone (or dose equivalent) within the last 14 consecutive days prior to VB10.16 treatment start Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or plasma components ≤2 weeks prior to VB10.16 treatment start 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) Has received prior surgery or prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment Any planned major surgery PRIOR OR CONCURRENT MORBIDITY Malignancy: Past or current malignancy other than inclusion diagnosis, except for: Cervical carcinoma, stage 1B or less Noninvasive basal cell or squamous cell skin carcinoma Noninvasive, superficial bladder cancer Prostate cancer with a current prostate-specific antigen level <0.1 ng/mL Any curable cancer with a complete response of >2 years' duration Hepatic and hemostatic function: Any current bleeding disorder, active bleeding, or bleeding diathesis Cardiovascular function: Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), despite optimal medical management Any other significant cardiac disease(s) that, in the opinion of the investigator, is/are clinically significant and/or unacceptable Pulmonary function: 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: Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression 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 Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by a local health authority 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 Any active, acute, or chronic infection that is uncontrolled and/or requires systemic treatment Known allergies, sensitivity, or intolerance to drug excipients, or aminoglycosides (especially kanamycin). Central nervous system (CNS) function: Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke 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 New (≤6 months), progressive and/or symptomatic brain metastases OTHER Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment 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 Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial 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 Female patients who are pregnant or breastfeeding

Sites / Locations

  • East and North Hertfordshire NHS Trust Mount Vernon HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab

Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab

Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab

Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab

Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab

Arm Description

3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions

6 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps or gluteus muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions

9 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle Pembrolizumab will be given as standard of care/ background medication via i.v. infusions

The highest dose of VB10.16 to be safety-cleared in the escalation phase will be given via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle Pembrolizumab will be given as standard of care/ background medication via i.v. infusions

3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions

Outcomes

Primary Outcome Measures

Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)
Proportion of patient with Dose Limiting Toxicities (DLTs).
Phase 2: Dose Expansion: AEs
Proportion of patients with AEs following treatment initiation by severity grade.
Phase 2: Dose Expansion: Discontinuation due to adverse reaction
Proportion of patients who discontinue due to an adverse reaction.
Phase 2: Dose Expansion: Objective Response Rate (ORR)
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
Phase 2: Dose Expansion: Immune response
Proportion of patients with increased HPV16 E6/E7-specific cellular immune responses from baseline as measured by E6/E7-IFN-γ ELISpot in post-vaccination samples.
Phase 1+2: Full trial: Objective Response Rate (ORR)
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response (BOR) per RECIST 1.1.
Phase 1+2: Full trial: Objective Response Rate (ORR)
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
Phase 1+2: Full trial: Duration of response (DOR)
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Phase 1+2: Full trial: Duration of response (DOR)
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Phase 1+2: Full trial: Progression-free survival (PFS)
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Phase 1+2: Full trial: Progression-free survival (PFS)
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Phase 1+2: Full trial: Proportion Progression-free
Proportion of patients who progression-free and alive.
Phase 1+2: Full trial: Proportion Progression-free
Proportion of patients who are progression-free and alive.
Phase 1 + 2: Full trial: Overall survival (OS)
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Phase 1 + 2: Full trial: Overall survival (OS)
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Phase 1 + 2: Full trial: Proportion alive
Proportion of patients who are alive.
Phase 1 + 2: Full trial: Proportion alive
Proportion of patients who are alive.

Secondary Outcome Measures

Phase 2: Dose Expansion: Disease control rate (DCR)
Disease control rate (DCR), defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as BOR according to RECIST 1.1.
Phase 2: Dose Expansion: Duration of response (DOR)
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Phase 2: Dose Expansion: Duration of complete response (DOCR)
Duration of complete response (DOCR), defined as time from the date of first documented response of CR to the date of the first documented progression or death due to any cause.
Phase 2: Dose Expansion: Duration of Disease Control (DODC)
Duration of Disease Control (DODC), defined as time from the date of first documented response of CR, PR or SD to the date of the first documented progression or death due to any cause.
Phase 2: Dose Expansion: Time to Response (TTR)
Time to Response (TTR), s defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.
Phase 2: Dose Expansion: Progression-free survival (PFS)
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Phase 2: Dose Expansion: Overall Survival (OS)
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Phase 2: Proportion of progression-free
Proportion of patients who are progression-free and alive.
Phase 2: Proportion of progression-free
Proportion of patients who are progression-free and alive.
Phase 2: Patients alive
Proportion of patients who are alive.
Phase 2: Patients alive
Proportion of patients who are alive.
Phase 1+2: Full trial: AEs following treatment initiation
Proportion of patients with AEs following treatment initiation by severity grade.
Phase 1+2: Full trial: AEs following treatment initiation
Proportion of patients with AEs following treatment initiation by severity grade.
Phase 1+2: Discontinuation due to an adverse reaction
Proportion of patients who discontinue due to an adverse reaction.
Phase 1+2: Discontinuation due to an adverse reaction
Proportion of patients who discontinue due to an adverse reaction.

Full Information

First Posted
August 24, 2023
Last Updated
September 29, 2023
Sponsor
Nykode Therapeutics ASA
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT06016920
Brief Title
Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma
Official Title
A Phase 1/2a, Open-label, Dose-finding Trial to Evaluate Safety, Immunogenicity, and Anti-tumor Activity of VB10.16 and Pembrolizumab in Patients With Unresectable Recurrent or Metastatic HPV16-positive Head-Neck Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
January 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nykode Therapeutics ASA
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a multi-center study in patients with un-resectable Recurrent or Metastatic HPV16-positive 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV-Related Squamous Cell Carcinoma, HNSCC
Keywords
Unresectable, recurrent, metastatic, HPV16 positive, PD-L1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
Arm Type
Experimental
Arm Description
3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Arm Title
Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
Arm Type
Experimental
Arm Description
6 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps or gluteus muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Arm Title
Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
Arm Type
Experimental
Arm Description
9 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Arm Title
Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
Arm Type
Experimental
Arm Description
The highest dose of VB10.16 to be safety-cleared in the escalation phase will be given via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Arm Title
Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
Arm Type
Experimental
Arm Description
3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
Intervention Type
Biological
Intervention Name(s)
VB10.16
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA
Intervention 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.
Primary Outcome Measure Information:
Title
Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)
Description
Proportion of patient with Dose Limiting Toxicities (DLTs).
Time Frame
42 days
Title
Phase 2: Dose Expansion: AEs
Description
Proportion of patients with AEs following treatment initiation by severity grade.
Time Frame
50 Weeks
Title
Phase 2: Dose Expansion: Discontinuation due to adverse reaction
Description
Proportion of patients who discontinue due to an adverse reaction.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Objective Response Rate (ORR)
Description
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Immune response
Description
Proportion of patients with increased HPV16 E6/E7-specific cellular immune responses from baseline as measured by E6/E7-IFN-γ ELISpot in post-vaccination samples.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: Objective Response Rate (ORR)
Description
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response (BOR) per RECIST 1.1.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: Objective Response Rate (ORR)
Description
Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
Time Frame
103 weeks
Title
Phase 1+2: Full trial: Duration of response (DOR)
Description
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: Duration of response (DOR)
Description
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Time Frame
103 weeks
Title
Phase 1+2: Full trial: Progression-free survival (PFS)
Description
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: Progression-free survival (PFS)
Description
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Time Frame
103 weeks
Title
Phase 1+2: Full trial: Proportion Progression-free
Description
Proportion of patients who progression-free and alive.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: Proportion Progression-free
Description
Proportion of patients who are progression-free and alive.
Time Frame
103 weeks
Title
Phase 1 + 2: Full trial: Overall survival (OS)
Description
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Time Frame
50 weeks
Title
Phase 1 + 2: Full trial: Overall survival (OS)
Description
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Time Frame
103 weeks
Title
Phase 1 + 2: Full trial: Proportion alive
Description
Proportion of patients who are alive.
Time Frame
50 weeks
Title
Phase 1 + 2: Full trial: Proportion alive
Description
Proportion of patients who are alive.
Time Frame
103 weeks
Secondary Outcome Measure Information:
Title
Phase 2: Dose Expansion: Disease control rate (DCR)
Description
Disease control rate (DCR), defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as BOR according to RECIST 1.1.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Duration of response (DOR)
Description
Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Duration of complete response (DOCR)
Description
Duration of complete response (DOCR), defined as time from the date of first documented response of CR to the date of the first documented progression or death due to any cause.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Duration of Disease Control (DODC)
Description
Duration of Disease Control (DODC), defined as time from the date of first documented response of CR, PR or SD to the date of the first documented progression or death due to any cause.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Time to Response (TTR)
Description
Time to Response (TTR), s defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Progression-free survival (PFS)
Description
Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
Time Frame
50 weeks
Title
Phase 2: Dose Expansion: Overall Survival (OS)
Description
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Time Frame
50 weeks
Title
Phase 2: Proportion of progression-free
Description
Proportion of patients who are progression-free and alive.
Time Frame
26 weeks
Title
Phase 2: Proportion of progression-free
Description
Proportion of patients who are progression-free and alive.
Time Frame
50 weeks
Title
Phase 2: Patients alive
Description
Proportion of patients who are alive.
Time Frame
26 weeks
Title
Phase 2: Patients alive
Description
Proportion of patients who are alive.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: AEs following treatment initiation
Description
Proportion of patients with AEs following treatment initiation by severity grade.
Time Frame
50 weeks
Title
Phase 1+2: Full trial: AEs following treatment initiation
Description
Proportion of patients with AEs following treatment initiation by severity grade.
Time Frame
103 weeks
Title
Phase 1+2: Discontinuation due to an adverse reaction
Description
Proportion of patients who discontinue due to an adverse reaction.
Time Frame
50 weeks
Title
Phase 1+2: Discontinuation due to an adverse reaction
Description
Proportion of patients who discontinue due to an adverse reaction.
Time Frame
103 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: GENERAL REQUIREMENTS ≥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) Histologically or cytologically confirmed R/M HNSCC considered incurable by local therapy and eligible for monotherapy with pembrolizumab HPV16 positivity of R/M HNSCC confirmed by designated central laboratory PD-L1 positivity (CPS ≥1) Must provide a tumor tissue sample collected prior to VB10.16 treatment initiation for baseline tumor microenvironment analyses Primary tumor location in the oropharynx, oral cavity, hypopharynx, or larynx At least 1 measurable lesion per RECIST 1.1 ORGAN FUNCTION Overall function: Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 Hematological function: Platelets 100 - 400 × 10^9/L (100,000 - 400,000/µL) Neutrophils (absolute neutrophil count [ANC]) ≥1.5 × 10^9/L (1,500/µL) Hemoglobin ≥5.6 mmol/L (9.0 g/dL) Hepatic and hemostatic function: Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome, then direct BILI ≤2 × ULN) Aspartate transaminase (AST) ≤ 2.5 × ULN Alanine transaminase (ALT) ≤ 2.5 × ULN Alkaline phosphatase ≤ 2.5 × ULN International normalized ratio (INR) ≤1.5 × ULN Renal function: Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m^2 using the Cockroft-Gault formula OTHER TRIAL REQUIREMENTS Female patients of childbearing potential: negative serum pregnancy test (≤72 hours) Female patients of childbearing potential and male patients must agree to use highly effective contraception, and male patients must refrain from sperm donation throughout the trial (14 days prior to initiation of treatment for oral contraception), and for at least 120 days (according to the latest country-specific pembrolizumab label) after the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16, whichever comes last 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 Has disease that is suitable for local therapy with curative intent Has progressive disease ≤6 months after completion of curatively intended systemic treatment for locoregionally advanced R/M HNSCC Primary tumor site of the nasopharynx (any histology) Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS Has received prior radiotherapy within 2 weeks of start of trial treatment or has had a history of radiation pneumonitis 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 Prior solid organ or tissue transplantation (except corneal transplant) Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) Prior chimeric antigen receptor T (CAR-T) cell therapy Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other molecule with similar mechanism of action) that engages T-cells Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial intervention Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start Prior administration with a therapeutic HPV16 vaccine Patients receiving systemic immunosuppression with immunosuppressive agents such as cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α) blockers for any concurrent condition Chronic administration of systemic corticosteroids: prednisone >10 mg daily (or dose equivalent) or an average cumulative dose of >140 mg prednisone (or dose equivalent) within the last 14 consecutive days prior to VB10.16 treatment start Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or plasma components ≤2 weeks prior to VB10.16 treatment start 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) Has received prior surgery or prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment Any planned major surgery PRIOR OR CONCURRENT MORBIDITY Malignancy: Past or current malignancy other than inclusion diagnosis, except for: Cervical carcinoma, stage 1B or less Noninvasive basal cell or squamous cell skin carcinoma Noninvasive, superficial bladder cancer Prostate cancer with a current prostate-specific antigen level <0.1 ng/mL Any curable cancer with a complete response of >2 years' duration Hepatic and hemostatic function: Any current bleeding disorder, active bleeding, or bleeding diathesis Cardiovascular function: Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), despite optimal medical management Any other significant cardiac disease(s) that, in the opinion of the investigator, is/are clinically significant and/or unacceptable Pulmonary function: 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: Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of immunosuppression 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 Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by a local health authority 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 Any active, acute, or chronic infection that is uncontrolled and/or requires systemic treatment Known allergies, sensitivity, or intolerance to drug excipients, or aminoglycosides (especially kanamycin). Central nervous system (CNS) function: Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke 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 New (≤6 months), progressive and/or symptomatic brain metastases OTHER Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment 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 Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the trial 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 Female patients who are pregnant or breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chief Medical Officer
Phone
+47 951 133 93
Email
storhaug@nykode.com
First Name & Middle Initial & Last Name or Official Title & Degree
Senior Clinical Trial Manager
Phone
+47 970 695 95
Email
lfinnesand@nykode.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Åse Bratland, MD, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
East and North Hertfordshire NHS Trust Mount Vernon Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saira Khalique, Dr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma

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