Clinical trial NCT04405349: Investigating the Combination of VB10.16 and Atezolizumab in Patients With HPV 16-positive Cervical Cancer
Official title: A Multi-Centre, Open-label Phase 2a Trial of the Combination of VB10.16 and Atezolizumab in Patients With Advanced or Recurrent, Non-resectable HPV 16-Positive Cervical Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Cervix Cancer
Keywords: Metastatic
Recurrent
Lead sponsor: Nykode Therapeutics ASA
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
name: Vaccibody AS
First posted: 2020-05-28
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and severity of adverse events (AEs)
timeFrame: 48 weeks (1 year follow-up)
measure: Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study
timeFrame: 48 weeks (1 year follow-up)
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: 48 weeks (1 year follow-up)
measure: Progression-free survival (PFS)
timeFrame: 48 weeks (1 year follow-up)
measure: Overall survival (OS)
timeFrame: 48 weeks (1 year follow-up)
measure: Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses
timeFrame: 48 weeks (1 year follow-up)
Other outcomes:
measure: 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
timeFrame: 48 weeks (1 year follow-up)
measure: Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1
timeFrame: 48 weeks (1 year follow-up)
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Hopital de Libramont
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent (Uz Gent)
city: Namur
country: Belgium
facility: Chu Ucl Namur
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment for Women's Health - Nadezhda Sofia
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Serdika"" EOOD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment Sofiamed
city: Brno
country: Czechia
facility: Masaryk Memorial Cancer Institute
city: Pardubice
country: Czechia
facility: Nemocnice Pardubickeho Kraje Pardubicka Nemocnice
city: Praha
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: Nemocnice Na Bulovce
city: Augsburg
country: Germany
facility: Universitatsklinikum Augsburg
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Medizinische Fakulat Mannheim Der Universitat Heidelberg
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Kraków
country: Poland
facility: Jagielońskie Centum Innowacji, Centrum Badań Klinicznych JCI
city: Poznań
country: Poland
facility: Wielkopolskie Centrum Onkologii
city: Warsaw
country: Poland
facility: 'Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie
Study officials:
affiliation: Nykode Therapeutics ASA
name: Siri Torhaug, MD
role: STUDY_DIRECTOR
References: