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

ConditionsHPV Positive Oropharyngeal Squamous Cell Carcinoma HNSCC

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorNykode Therapeutics ASA

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

≥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, located in the oropharynx, considered incurable by local therapy and eligible for monotherapy with pembrolizumab

HPV16 positivity of R/M oropharyngeal HNSCC confirmed by designated central laboratory

PD-L1 positivity (CPS ≥1) using the validated PD-L1 IHC 22C3 pharmDx (DAKO) assay.

Disqualifiers

Has disease that is suitable for local therapy with curative intent

Has progressive disease ≤6 months after completion of curatively intended concurrent chemoradiotherapy for locoregionally advanced R/M oropharyngeal HNSCC

Primary tumor site of the oral cavity, hypopharynx, larynx or nasopharynx (any histology)

Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator

Trial design

Design model

Sequential

Treatments tested in this trial

VB10.16
Biological/Vaccine
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.
Pembrolizumab
Drug
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.

Treatment groups

51 Participants

are divided into 5 treatment groups

Group A: Phase1: Dose Escalation: 3 mg VB10.16 + PembrolizumabExperimental treatment 2 interventions

Group B: Phase 1: Dose Escalation: 6 mg VB10.16 + PembrolizumabExperimental treatment 2 interventions

Group C: Phase 1: Dose Escalation: 9 mg VB10.16 + PembrolizumabExperimental treatment 2 interventions

Group D: Phase 2: Dose Expansion: High dose of VB10.16 + PembrolizumabExperimental treatment 2 interventions

Group E: Phase 2: Dose Expansion: 3 mg VB10.16 + PembrolizumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)

Proportion of patient with Dose Limiting Toxicities (DLTs).

Time frame

42 days

Phase 2: Dose Expansion: AEs

Proportion of patients with AEs following treatment initiation by severity grade.

Time frame

12 months

Phase 2: Dose Expansion: Discontinuation due to adverse reaction

Proportion of patients who discontinue due to an adverse reaction.

Time frame

12 months

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.

Time frame

12 months

Secondary outcomes

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.

Time frame

12 months

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.

Time frame

12 months

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.

Time frame

24 months

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.

Time frame

12 months