Investigating the Combination of VB10.16 and Atezolizumab in Patients With HPV 16-positive Cervical Cancer

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04405349
• Other study ID #: VB C-02
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2020
• Est. completion date: November 24, 2023

Study information

• Verified date: December 2023
• Source: Nykode Therapeutics ASA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 24, 2023
• Est. primary completion date: November 24, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervical Cancer
• Cervix Cancer
• Uterine Cervical Neoplasms

Intervention

Biological:
• VB10.16
Vaccination
• Atezolizumab
Intravenously infusion

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Hopital de Libramont	Bruxelles
Belgium	Universitair Ziekenhuis Gent (Uz Gent)	Gent
Belgium	Chu Ucl Namur	Namur
Bulgaria	Multiprofile Hospital for Active Treatment "Serdika"" EOOD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment for Women's Health - Nadezhda Sofia	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"	Sofia
Bulgaria	University Multiprofile Hospital For Active Treatment Sofiamed	Sofia
Czechia	Masaryk Memorial Cancer Institute	Brno
Czechia	Nemocnice Pardubickeho Kraje Pardubicka Nemocnice	Pardubice
Czechia	Nemocnice Na Bulovce	Praha
Czechia	University Hospital Kralovske Vinohrady	Praha
Germany	Universitatsklinikum Augsburg	Augsburg
Germany	University Clinic Carl Gustav Carus	Dresden
Germany	Universitatsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Medizinische Fakulat Mannheim Der Universitat Heidelberg	Heidelberg
Norway	Oslo University Hospital	Oslo
Poland	Jagielonskie Centum Innowacji, Centrum Badan Klinicznych JCI	Kraków
Poland	Wielkopolskie Centrum Onkologii	Poznan
Poland	'Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Warsaw

Sponsors (3)

Lead Sponsor	Collaborator
Nykode Therapeutics ASA	Roche Pharma AG, Vaccibody AS

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Czechia,  Germany,  Norway,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	T cell infiltration, PD-L1 expression or other immune-oncology related genes	48 weeks (1 year follow-up)
Other	Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1	ctDNA	48 weeks (1 year follow-up)
Primary	Incidence and severity of adverse events (AEs)	The number and percentage of participants that experience an adverse event (AE	48 weeks (1 year follow-up)
Primary	Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study	ORR as assessed by RECIST v1.1	48 weeks (1 year follow-up)
Secondary	Duration of response (DOR)	Estimate the duration of response (DOR) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
Secondary	Progression-free survival (PFS)	Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
Secondary	Overall survival (OS)	Overall survival (OS) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
Secondary	Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses	Systemic T-cell response	48 weeks (1 year follow-up)