This is a multi-center study in patients with recurrent or metastatic HPV16-positive, PD-L1 positive cervical cancer who has progressed during or after treatment with the first-line standard of care (pembrolizumab with chemotherapy with/without bevacizumab). The trial is designed to investigate VB10.16 alone or in combination with the immune checkpoint inhibitor, atezolizumab. The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the best. The second part of the study will select the best treatment from part 1 and investigate the safety and efficacy of additional 70 patients.
This is a two-arm randomized, double-blind, placebo-controlled phase 2 selection trial to evaluate the efficacy and safety of VB10.16 alone or in combination with atezolizumab in patients with HPV16-positive, PD-L1-positive, recurrent or metastatic cervical cancer who are refractory to pembrolizumab with chemotherapy with/without bevacizumab. A selection design with a margin of practical equivalence will be implemented to monitor efficacy of the two experimental arms (VB10.16 + atezolizumab vs. VB10.16 + placebo). The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the superior. The second part of the study will select the superior treatment from part 1 and investigate the safety and efficacy of additional 70 patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 49. A total of up to 11 i.m. administrations will be given. VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.
Intravenous (IV) infusions of atezolizumab (saline solution) every 3 weeks.
Intravenous (IV) infusions of placebo (saline solution) every 3 weeks.
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 as assessed by blinded independent central review (BICR).
Time frame: Up to 1 year
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 as assessed by the investigator.
Time frame: Up to approximately 2 year
Duration of Response (DOR)
Duration of response (DOR) based upon RECIST v1.1 assessed by BICR. DOR is defined as time from the date of first documented response of confirmed CR or PR to the date of the first documented progression or death due to any cause, whichever occur first.
Time frame: Up to approximately 2 years
Duration of Response (DOR)
Duration of response (DOR) based upon RECIST v1.1 assessed by the investigator. DOR is defined as time from the date of first documented response of confirmed CR or PR to the date of the first documented progression or death due to any cause, whichever occur first.
Time frame: Up to approximately 2 years
Time to Response (TTR)
Time to response (TTR) based upon RECIST v1.1 assessed by BICR. TTR is 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: Up to approximately 2 years
Disease Control Rate (DCR)
Disease Control Rate (DCR) based upon RECIST v1.1 assessed by BICR. DCR is defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as best overall response.
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Time frame: Up to approximately 2 years
Duration of Disease Control (DODC)
Duration of disease control (DODC) based upon RECIST v1.1 assessed by BICR. DODC is defined as time from the date of first documented response of confirmed CR, confirmed PR or SD to the date of the first documented progression or death due to any cause.
Time frame: Up to approximately 2 years
Progression Free Survival (PFS)
Progression-free survival (PFS) as assessed by BICR. PFS is 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: Up to approximately 2 years
Progression Free Survival (PFS)
Progression-free survival (PFS) as assessed by the investigator. PFS is 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: Up to approximately 2 years
Overall survival (OS)
Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
Time frame: Up to approximately 2 years
Minimal Response
Proportion of participants with tumor shrinkage ≥10.0% to \<30% assessed by BICR.
Time frame: Up to approximately 2 years
Proportion of participants who are Progression-free
Proportion of participants who are progression-free and alive based upon RECIST v1.1 assessed by BICR.
Time frame: 26 weeks
Proportion of participants who are Progression-free
Proportion of participants who are progression-free and alive based upon RECIST v1.1 assessed by BICR.
Time frame: 52 weeks
Proportion of participants who are Progression-free
Proportion of participants who are progression-free and alive based upon RECIST v1.1 assessed by BICR.
Time frame: 104 weeks
Proportion of participants who are alive.
Proportion of participants who are alive.
Time frame: 26 weeks
Proportion of participants who are alive.
Proportion of participants who are alive.
Time frame: 52 weeks
Proportion of participants who are alive.
Proportion of participants who are alive.
Time frame: 104 weeks
Molecular Response
Proportion of participants with molecular response defined as ≥30% decrease from baseline in HPV16 ctDNA.
Time frame: Up to week 52
Molecular Response
Proportion of participants with molecular response defined as ≥50% decrease from baseline in HPV16 ctDNA.
Time frame: Up to week 52
Proportion of participants with treatment emergent adverse events
Proportion of participants with treatment-emergent adverse events (TEAEs) by severity grade.
Time frame: Up to week 104
Proportion of participants with treatment-emergent serious adverse events
Proportion of participants with treatment-emergent serious adverse events
Time frame: Up to week 104
Proportion of participants with drug related toxicity
Proportion of participants with drug-related toxicity of CTCAE grade ≥3
Time frame: Up to week 104
Proportion of participants with discontinuation
Proportion of participants discontinuing treatment due to an adverse reaction.
Time frame: Up to week 104