Cervical Cancer, Cervix Cancer
Conditions
Keywords
Metastatic, Recurrent
Brief summary
This phase IIa study is designed to evaluate the safety and efficacy of multiple dosing with VB10.16 immunotherapy in combination with atezolizumab in patients with advanced or recurrent non-resectable HPV16-positive cervical cancer, who failed or are not eligible for current standard of care.
Detailed description
Patients will receive up to 11 intramuscular (i.m.) vaccinations of VB10.16, for up to 48 weeks from first vaccination. Patients will receive 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks from first immunisation (total of 11 vaccinations). Patients will receive up to 17 infusions of atezolizumab for up to 48 weeks from first treatment. Atezolizumab (1200 mg) will be administered as an intravenous (i.v.) infusion every 3 weeks. A follow-up period of up to 12 months will follow the 48 week treatment period. Response to the VB10.16 and atezolizumab combination will be assessed by computed tomography (CT)/magnetic resonance imaging (MRI) at every 9 weeks throughout the treatment period according to the RECIST 1.1 criteria.
Interventions
BIOLOGICALVB10.16
Vaccination
BIOLOGICALAtezolizumab
Intravenously infusion
Sponsors
Roche Pharma AG
Vaccibody AS
Nykode Therapeutics ASA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has persistent, recurrent, or metastatic non-resectable squamous cell carcinoma, adeno-squamous carcinoma, or adenocarcinoma of the cervix, who has failed or is not eligible for treatment with systemic chemotherapy, radiotherapy or other standard-of-care anticancer treatment. 2. Tumour must be HPV16 positive. Provision of an archival tumour tissue sample not older than 2 years or new biopsy for analysing HPV16 status is mandatory. 3. Must have a biopsy (archived or new) available for PD L1 assessment at Screening. 4. Has measurable disease as assessed by the local site investigator/radiology as per RECIST 1.1. 5. Has recovered from the effects of surgery, radiation therapy, or chemoradiotherapy. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at Screening. 7. Is aged 18 years or older. 8. Has life expectancy of at least 6 months in the best judgement of the investigator. 9. Is willing and able to sign a written informed consent form.
Exclusion criteria
1. Patients who, in the investigator's opinion, have progressed rapidly on their previous anticancer treatment (e.g., did not achieve any response \[CR, PR, or SD\]). 2. Has brain metastases (unless they have received prior treatment and are controlled and stable for at least 6 weeks before study enrolment) or leptomeningeal spread of disease. 3. Has positive serological test for hepatitis C virus (HCV), hepatitis B virus (HBV), surface antigen (HBsAg), positive HBV core antibody. Human immunodeficiency virus (HIV). 4. Has other concomitant or prior malignant disease, 5. Has an active, known or suspected autoimmune disease. 6. Is receiving systemic immunosuppression including systemic steroids or the use of immunosuppressive agents for any concurrent condition. 7. Has known allergy to aminoglycosides or kanamycin or any study treatment component. 8. Has history of toxic shock syndrome. 9. Has history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organising pneumonia, immune enteritis or active pneumonitis. 10. Has evidence or history of clinically significant cardiac disease including congestive heart failure 11. Has ongoing toxicity from prior therapy 12. Has severe infections within 4 weeks prior to study start 13. Current participation in a clinical trial 14. Has received investigational drug within 30 days before study entry. 15. Has received vaccination against infections within 30 days before study entry. 16. Has had prior treatment with CD137, anti-PD-1, or anti-PD-L1 therapeutic antibody or other immune checkpoint targeting agents. 17. Has known hypersensitivity to any component of the atezolizumab or VB10.16 formulation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AEs) | 48 weeks (1 year follow-up) | The number and percentage of participants that experience an adverse event (AE |
| Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study | 48 weeks (1 year follow-up) | ORR as assessed by RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 48 weeks (1 year follow-up) | Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer |
| Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses | 48 weeks (1 year follow-up) | Systemic T-cell response |
| Overall survival (OS) | 48 weeks (1 year follow-up) | Overall survival (OS) in patients with advanced cervical cancer |
| Duration of response (DOR) | 48 weeks (1 year follow-up) | Estimate the duration of response (DOR) in patients with advanced cervical cancer |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assess predictive biomarkers, such as programmed death-ligand 1 (PD-L1) in tumour material and investigate changes in tumour microenvironment by immunohistochemistry (IHC) and/or gene expression | 48 weeks (1 year follow-up) | T cell infiltration, PD-L1 expression or other immune-oncology related genes |
| Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1 | 48 weeks (1 year follow-up) | ctDNA |
Countries
Belgium, Bulgaria, Czechia, Germany, Norway, Poland
Outcome results
None listed