Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Cemiplimab

Antineoplastic Agents, Immunological

ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months

Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months

ISA101b

Placebo

Bonnie S. Glisson, MD, BS

This will be a blinded, placebo-controlled, randomized, phase 2 study in which subjects will be randomly assigned 1:1 to cemiplimab plus placebo or cemiplimab plus ISA101b.

This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with HPV16 positive OPC, when combined with cemiplimab, an investigational anti-PD-1 antibody being developed by Regeneron Pharmaceuticals. ISA101b is a therapeutic cancer vaccine that induces specific immune responses to the oncogenic E6 and E7 antigens from HPV16. Trials in HPV16 driven malignancies indicate it has activity in HPV16 driven malignancies including oropharyngeal and cervical cancers. Cemiplimab, also known as REGN2810, is in late stage trials and appears to have similar activity to approved anti PD-1 antibodies in a number of malignancies .

A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC

A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study of Cemiplimab Versus the Combination of Cemiplimab With ISA101b in the Treatment of Subjects With HPV16-Positive Oropharyngeal Cancer (OPC)

Regeneron Pharmaceuticals

ISA Pharmaceuticals

Symptoms and General Pathology

Recurrence

Pembrolizumab

Immune Checkpoint Inhibitors

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

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.

VB10.16

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.

Chief Medical Officer

Senior Clinical Trial Manager

Melichar Bohuslav

Jonathan Thouvenin

Caroline Even

Andreas Dietz

Erika Hitre, MD

Marianne Brydoy, MD

Åse Bratland, MD, PhD

Rafal Dziadziusczko, Dr

Tomasz Rutkowski, Dr

Ludmilla Grzybowska - Szatkowska

Marta Guix Arnau

Marc Oliva

Juaquina Martin Galan

Pilar López Criado

Saira Khalique, Dr

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.

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.

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

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

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

Proportion of patient with Dose Limiting Toxicities (DLTs).

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

Proportion of patients who discontinue due to an adverse reaction.

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.

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.

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.

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.

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.

Proportion of patients who progression-free and alive.

Proportion of patients who are progression-free and alive.

Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.

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.

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.

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 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Randomized Phase 2 Study of Cemiplimab ± ISA101b in HPV16-Positive OPC	NCT03669718	Squamous Cell C... HPV16 Positive	ISA101b Cemiplimab Placebo	18 Years -	ISA Pharmaceuticals
Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma	NCT06016920	HPV-Related Squ... HNSCC	VB10.16 Pembrolizumab	18 Years -	Nykode Therapeutics ASA

Spots Global Cancer Trial Database for hpv16 positive