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

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Cervix Cancer
• Intervention / Treatment: Biological: VB10.16; Biological: Atezolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Bruxelles, Belgium, 1200
    • Hopital De Libramont
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent (UZ Gent)
  • Namur, Belgium, 5000
    • CHU UCL Namur
• Bulgaria
  • Sofia, Bulgaria, 1330
    • Multiprofile Hospital for Active Treatment for Women's Health - Nadezhda Sofia
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"
  • Sofia, Bulgaria, 1527
    • Multiprofile Hospital for Active Treatment "Serdika"" EOOD
  • Sofia, Bulgaria, 1797
    • University Multiprofile Hospital for Active Treatment Sofiamed
• Czechia
  • Brno, Czechia, 65653
    • Masaryk Memorial Cancer Institute
  • Pardubice, Czechia, 53203
    • Nemocnice Pardubickeho Kraje Pardubicka Nemocnice
  • Praha, Czechia, 10034
    • University Hospital Kralovske Vinohrady
  • Praha, Czechia, 180 81
    • Nemocnice Na Bulovce
• Germany
  • Augsburg, Germany
    • Universitatsklinikum Augsburg
  • Dresden, Germany
    • University Clinic Carl Gustav Carus
  • Hamburg, Germany
    • Universitatsklinikum Hamburg-Eppendorf
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Medizinische Fakulat Mannheim Der Universitat Heidelberg
• Norway
  • Oslo, Norway, 0379
    • Oslo University Hospital
• Poland
  • Kraków, Poland
    • Jagielońskie Centum Innowacji, Centrum Badań Klinicznych JCI
  • Poznań, Poland
    • Wielkopolskie Centrum Onkologii
  • Warsaw, Poland
    • 'Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Therapy; VB10.16 vaccinations. 11 intramuscular (i.m.) vaccinations for up to 48 weeks from first vaccination. 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks + Atezolizumab (1200 mg) intravenous (i.v.) infusion every 3 weeks.	Biological: VB10.16; Vaccination; Biological: Atezolizumab; Intravenously infusion; Other Names: Tecentriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	Estimate the duration of response (DOR) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
Progression-free survival (PFS)	Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
Overall survival (OS)	Overall survival (OS) in patients with advanced cervical cancer	48 weeks (1 year follow-up)
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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1	ctDNA	48 weeks (1 year follow-up)

Collaborators and Investigators

• Sponsor: Nykode Therapeutics ASA
• Collaborators: Roche Pharma AG; Vaccibody AS
• Investigators: Study Director: Siri Torhaug, MD, Nykode Therapeutics ASA

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): November 24, 2023
• Study Completion (Actual): November 24, 2023

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Metastatic; Recurrent
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: VB C-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No